Abstract
In contrast to non-mammalian vertebrates, mammals and humans have limited innate capacity for the self-regeneration of tissues and organs owing to differences in genetics, development, immune systems and tissue complexity. Endogenous stem cells are tissue-specific adult stem cells with the capacity to self-renew and differentiate into specific cell types. Therefore, endogenous stem cells are being explored for the regeneration of tissues in situ and in vivo. Stem cells reside in specific niches in the body, and stem cell activation depends on progressive changes in the niche. Niches are specific and instructive microenvironments that can be recreated using biomaterial-based scaffolds. Such scaffolds can be fabricated into a variety of shapes and formulations, and they can be functionalized with biochemical and biophysical cues to guide stem cell fate and migration. In this Review, we discuss important differences in the self-regeneration abilities of non-mammalian vertebrates and mammals, including humans, and investigate adult stem cell populations and their niches involved in tissue repair and regeneration. We highlight natural and synthetic biomaterials and their potential for improving applications of endogenous stem cells and examine the role of interspecies chimaeras in regenerative medicine.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Change history
27 July 2018
This article was originally published with an incorrect affiliation 1. The correct affiliation 1 is: Department of Pediatric Surgery and Center for Genetic Diagnosis, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
References
Porrello, E. R. et al. Transient regenerative potential of the neonatal mouse heart. Science 331, 1078–1080 (2011).
Tsonis, P. A. & Fox, T. P. Regeneration according to Spallanzani. Dev. Dynam. 238, 2357–2363 (2009).
Michalopoulos, G. K. Liver regeneration. J. Cell. Physiol. 213, 286–300 (2007).
Thomas, E. D., Lochte, H. L. Jr, Lu, W. C. & Ferrebee, J. W. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N. Engl. J. Med. 257, 491–496 (1957).
Brockes, J. P. & Kumar, A. Comparative aspects of animal regeneration. Annu. Rev. Cell Dev. Biol. 24, 525–549 (2008).
Carlson, M. E. & Conboy, I. M. Regulating the Notch pathway in embryonic, adult and old stem cells. Curr. Opin. Pharmacol. 7, 303–309 (2007).
Tanaka, E. M. & Reddien, P. W. The cellular basis for animal regeneration. Dev. Cell 21, 172–185 (2011).
Godwin, J. W. & Rosenthal, N. Scar-free wound healing and regeneration in amphibians: immunological influences on regenerative success. Differentiation 87, 66–75 (2014).
Daar, A. S. & Greenwood, H. L. A proposed definition of regenerative medicine. J. Tissue Eng. Regen Med. 1, 179–184 (2007).
Lee, A. S., Tang, C., Rao, M. S., Weissman, I. L. & Wu, J. C. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nat. Med. 19, 998–1004 (2013).
Squillaro, T., Peluso, G. & Galderisi, U. Clinical trials with mesenchymal stem cells: an update. Cell Transplant 25, 829–848 (2016).
Lister, R. et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471, 68–73 (2011).
Amaya, E. Xenomics. Genome Res. 15, 1683–1691 (2005).
Harland, R. M. & Grainger, R. M. Xenopus research: metamorphosed by genetics and genomics. Trends Genet. 27, 507–515 (2011).
Yokoyama, H. et al. Prx-1 expression in Xenopus laevis scarless skin-wound healing and its resemblance to epimorphic regeneration. J. Invest. Dermatol. 131, 2477–2485 (2011).
Henry, J. J. & Tsonis, P. A. Molecular and cellular aspects of amphibian lens regeneration. Prog. Retin. Eye Res. 29, 543–555 (2010).
Bettencourt-Dias, M., Mittnacht, S. & Brockes, J. P. Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes. J. Cell Sci. 116, 4001–4009 (2003).
Love, N. R. et al. Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration. Bmc Dev. Biol. 11, 70 (2011).
Hui, S. P. et al. Zebrafish regulatory T cells mediate organ-specific regenerative programs. Dev. Cell 43, 659–672 (2017).
Rigamonti, E., Zordan, P., Sciorati, C., Rovere-Querini, P. & Brunelli, S. Macrophage plasticity in skeletal muscle repair. Biomed. Res. Int. 2014, 560629 (2014).
Iismaa, S. E. et al. Comparative regenerative mechanisms across different mammalian tissues. NPJ Regen. Med. 3, 6 (2018).
Petrie, T. A., Strand, N. S., Tsung-Yang, C., Rabinowitz, J. S. & Moon, R. T. Macrophages modulate adult zebrafish tail fin regeneration. Development 141, 2581–2591 (2014).
Banaei-Bouchareb, L. et al. Insulin cell mass is altered in Csf1op/Csf1op macrophage-deficient mice. J. Leukocyte Biol. 76, 359–367 (2004).
Lucas, T. et al. Differential roles of macrophages in diverse phases of skin repair. J. Immunol. 184, 3964–3977 (2010).
Godwin, J., Kuraitis, D. & Rosenthal, N. Extracellular matrix considerations for scar-free repair and regeneration: insights from regenerative diversity among vertebrates. Int. J. Biochem. Cell Biol. 56, 47–55 (2014).
Corona, B. T. et al. Autologous minced muscle grafts: a tissue engineering therapy for the volumetric loss of skeletal muscle. Am. J. Physiol. Cell Physiol. 305, C761–775 (2013).
Kishi, K., Okabe, K., Shimizu, R. & Kubota, Y. Fetal skin possesses the ability to regenerate completely: complete regeneration of skin. Keio J. Med. 61, 101–108 (2012).
Sattler, S. & Rosenthal, N. The neonate versus adult mammalian immune system in cardiac repair and regeneration. Biochim. Biophys. Acta 1863, 1813–1821 (2016).
Aurora, A. B. et al. Macrophages are required for neonatal heart regeneration. J. Clin. Invest. 124, 1382–1392 (2014).
Wilgus, T. A. Regenerative healing in fetal skin: a review of the literature. Ostomy Wound Manage. 53, 16–31; quiz 32–33 (2007).
Colwell, A. S., Longaker, M. T. & Lorenz, H. P. Fetal wound healing. Front. Biosci. 8, s1240–1248 (2003).
Lorenz, H. P., Lin, R. Y., Longaker, M. T., Whitby, D. J. & Adzick, N. S. The fetal fibroblast: the effector cell of scarless fetal skin repair. Plast. Reconstr Surg. 96, 1251–1259; discussion 1260–1261 (1995).
Colwell, A. S., Krummel, T. M., Longaker, M. T. & Lorenz, H. P. An in vivo mouse excisional wound model of scarless healing. Plast. Reconstr Surg. 117, 2292–2296 (2006).
Lorenz, H. P., Whitby, D. J., Longaker, M. T. & Adzick, N. S. Fetal wound healing. The ontogeny of scar formation in the non-human primate. Ann. Surg. 217, 391–396 (1993).
Peake, M. A. et al. Identification of a transcriptional signature for the wound healing continuum. Wound Repair Regen 22, 399–405 (2014).
Wulff, B. C. et al. Mast cells contribute to scar formation during fetal wound healing. J. Invest. Dermatol. 132, 458–465 (2012).
Wilgus, T. A., Ferreira, A. M., Oberyszyn, T. M., Bergdall, V. K. & Dipietro, L. A. Regulation of scar formation by vascular endothelial growth factor. Lab Invest. 88, 579–590 (2008).
Liechty, K. W., Adzick, N. S. & Crombleholme, T. M. Diminished interleukin 6 (IL-6) production during scarless human fetal wound repair. Cytokine 12, 671–676 (2000).
Liechty, K. W., Crombleholme, T. M., Cass, D. L., Martin, B. & Adzick, N. S. Diminished interleukin-8 (IL-8) production in the fetal wound healing response. J. Surg. Res. 77, 80–84 (1998).
Ozturk, S., Deveci, M., Sengezer, M. & Gunhan, O. Results of artificial inflammation in scarless foetal wound healing: an experimental study in foetal lambs. Br. J. Plast. Surg. 54, 47–52 (2001).
Gawronska-Kozak, B., Grabowska, A., Kopcewicz, M. & Kur, A. Animal models of skin regeneration. Reprod. Biol. 14, 61–67 (2014).
Sawai, T. et al. Hyaluronic acid of wound fluid in adult and fetal rabbits. J. Pediatr. Surg. 32, 41–43 (1997).
Ferguson, M. W. et al. Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies. Lancet 373, 1264–1274 (2009).
Seok, J. et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc. Natl Acad. Sci. USA 110, 3507–3512 (2013).
Fu, X. et al. Combination of inflammation-related cytokines promotes long-term muscle stem cell expansion. Cell Res. 25, 655–673 (2015).
Clevers, H. & Watt, F. M. Defining adult stem cells by function, not by phenotype. Annu. Rev. Biochem. https://doi.org/10.1146/annurev-biochem-062917-012341 (2018).
Lee, E. H. & Hui, J. H. The potential of stem cells in orthopaedic surgery. J. Bone Joint Surg. Br. 88, 841–851 (2006).
Lu, L., Finegold, M. J. & Johnson, R. L. Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration. Exp. Mol. Med. 50, e423 (2018).
Sackstein, R. et al. Ex vivo glycan engineering of CD44 programs human multipotent mesenchymal stromal cell trafficking to bone. Nat. Med. 14, 181–187 (2008).
De Coppi, P. et al. Isolation of amniotic stem cell lines with potential for therapy. Nat. Biotechnol. 25, 100–106 (2007).
Wang, H. S. et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22, 1330–1337 (2004).
Zuk, P. A. et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7, 211–228 (2001).
Horner, P. J. & Gage, F. H. Regenerating the damaged central nervous system. Nature 407, 963–970 (2000).
Caplan, A. I. Mesenchymal stem cells. J. Orthop. Res. 9, 641–650 (1991).
Tropepe, V. et al. Retinal stem cells in the adult mammalian eye. Science 287, 2032–2036 (2000).
Toma, J. G. et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat. Cell Biol. 3, 778–784 (2001).
Mohamed, T. M. A. et al. Regulation of cell cycle to stimulate adult cardiomyocyte proliferation and cardiac regeneration. Cell 173, 104–116 (2018).
Srivastava, D. & DeWitt, N. In vivo cellular reprogramming: the next generation. Cell 166, 1386–1396 (2016).
Mahla, R. S. Stem cells applications in regenerative medicine and disease therapeutics. Int. J. Cell Biol. 2016, 6940283 (2016).
Ankrum, J. & Karp, J. M. Mesenchymal stem cell therapy: two steps forward, one step back. Trends Mol. Med. 16, 203–209 (2010).
Dexter, T. M., Wright, E. G., Krizsa, F. & Lajtha, L. G. Regulation of haemopoietic stem cell proliferation in long term bone marrow cultures. Biomedicine 27, 344–349 (1977).
Allen, T. D. & Dexter, T. M. Ultrastructural aspects of erythropoietic differentiation in long-term bone marrow culture. Differentiation 21, 86–94 (1982).
Tavassoli, M. & Friedenstein, A. Hemopoietic stromal microenvironment. Am. J. Hematol. 15, 195–203 (1983).
Owen, M. & Friedenstein, A. J. Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found. Symp. 136, 42–60 (1988).
Gnecchi, M. & Melo, L. G. Bone marrow-derived mesenchymal stem cells: isolation, expansion, characterization, viral transduction, and production of conditioned medium. Methods Mol. Biol. 482, 281–294 (2009).
Friedenstein, A. J., Piatetzky, S., I. I. & Petrakova, K. V. Osteogenesis in transplants of bone marrow cells. J. Embryol. Exp. Morphol. 16, 381–390 (1966).
Owen, M. The origin of bone cells in the postnatal organism. Arthritis Rheum. 23, 1073–1080 (1980).
Owen, M. Marrow stromal stem cells. J. Cell Sci. Suppl. 10, 63–76 (1988).
Bruder, S. P., Fink, D. J. & Caplan, A. I. Mesenchymal stem cells in bone development, bone repair, and skeletal regeneration therapy. J. Cell. Biochem. 56, 283–294 (1994).
Caplan, A. I. Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. Tissue Eng. 11, 1198–1211 (2005).
Beresford, J. N., Graves, S. E. & Smoothy, C. A. Formation of mineralized nodules by bone derived cells in vitro: a model of bone formation? Am. J. Med. Genet. 45, 163–178 (1993).
Altman, G. H. et al. Silk matrix for tissue engineered anterior cruciate ligaments. Biomaterials 23, 4131–4141 (2002).
Beresford, J. N., Bennett, J. H., Devlin, C., Leboy, P. S. & Owen, M. E. Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J. Cell Sci. 102, 341–351 (1992).
Johnstone, B. & Yoo, J. U. Autologous mesenchymal progenitor cells in articular cartilage repair. Clin. Orthop. Relat. Res. 367, S156–S162 (1999).
Yoo, J. U. & Johnstone, B. The role of osteochondral progenitor cells in fracture repair. Clin. Orthop. Relat. Res. 355, S73–S81 (1998).
Wakitani, S., Saito, T. & Caplan, A. I. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 18, 1417–1426 (1995).
Friedenstein, A. J., Latzinik, N. W., Grosheva, A. G. & Gorskaya, U. F. Marrow microenvironment transfer by heterotopic transplantation of freshly isolated and cultured cells in porous sponges. Exp. Hematol. 10, 217–227 (1982).
Ashton, B. A. et al. Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clin. Orthop. Relat. Res. 151, 294–307 (1980).
Casser-Bette, M., Murray, A. B., Closs, E. I., Erfle, V. & Schmidt, J. Bone formation by osteoblast-like cells in a three-dimensional cell culture. Calcif. Tissue Int. 46, 46–56 (1990).
Wakitani, S. et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J. Bone Joint Surg. Am. 76, 579–592 (1994).
De Bari, C. et al. Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane. J. Cell Biol. 160, 909–918 (2003).
Salingcarnboriboon, R. et al. Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property. Exp. Cell Res. 287, 289–300 (2003).
Bosch, P. et al. Osteoprogenitor cells within skeletal muscle. J. Orthop. Res. 18, 933–944 (2000).
Zuk, P. A. et al. Human adipose tissue is a source of multipotent stem cells. Mol. Biol. Cell 13, 4279–4295 (2002).
Erickson, G. R. et al. Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. Biochem. Biophys. Res. Commun. 290, 763–769 (2002).
Dragoo, J. L. et al. Tissue-engineered cartilage and bone using stem cells from human infrapatellar fat pads. J. Bone Joint Surg. Br. 85, 740–747 (2003).
Kuznetsov, S. A. et al. Circulating skeletal stem cells. J. Cell Biol. 153, 1133–1140 (2001).
Trounson, A. & McDonald, C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17, 11–22 (2015).
Borlongan, C. V. Age of PISCES: stem-cell clinical trials in stroke. Lancet 388, 736–738 (2016).
Halvorsen, Y. D. et al. Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. Tissue Eng. 7, 729–741 (2001).
Strem, B. M. et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J. Med. 54, 132–141 (2005).
Huang, J. I. et al. Chondrogenic potential of multipotential cells from human adipose tissue. Plast. Reconstr Surg. 113, 585–594 (2004).
Rodriguez, A. M., Elabd, C., Amri, E. Z., Ailhaud, G. & Dani, C. The human adipose tissue is a source of multipotent stem cells. Biochimie 87, 125–128 (2005).
Seo, M. J., Suh, S. Y., Bae, Y. C. & Jung, J. S. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem. Biophys. Res. Commun. 328, 258–264 (2005).
Safford, K. M. et al. Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem. Biophys. Res. Commun. 294, 371–379 (2002).
Rangappa, S., Fen, C., Lee, E. H., Bongso, A. & Sim, E. K. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann. Thorac Surg. 75, 775–779 (2003).
Charriere, G. et al. Preadipocyte conversion to macrophage. Evidence of plasticity. J. Biol. Chem. 278, 9850–9855 (2003).
Tholpady, S. S. et al. Adipose tissue: stem cells and beyond. Clin. Plast. Surg. 33, 55–62 (2006).
Afizah, H., Yang, Z., Hui, J. H., Ouyang, H. W. & Lee, E. H. A comparison between the chondrogenic potential of human bone marrow stem cells (BMSCs) and adipose-derived stem cells (ADSCs) taken from the same donors. Tissue Eng. 13, 659–666 (2007).
Bartholomew, A. et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp. Hematol. 30, 42–48 (2002).
Rosenwald, A. et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B cell lymphoma. N. Engl. J. Med. 346, 1937–1947 (2002).
Puissant, B. et al. Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br. J. Haematol. 129, 118–129 (2005).
Lendeckel, S. et al. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. J. Craniomaxillofac. Surg. 32, 370–373 (2004).
Fu, X. & Sun, X. Can hematopoietic stem cells be an alternative source for skin regeneration? Ageing Res. Rev. 8, 244–249 (2009).
Inokuma, D. et al. CTACK/CCL27 accelerates skin regeneration via accumulation of bone marrow-derived keratinocytes. Stem Cells 24, 2810–2816 (2006).
Kroeze, K. L. et al. Chemokine-mediated migration of skin-derived stem cells: predominant role for CCL5/RANTES. J. Invest. Dermatol. 129, 1569–1581 (2009).
Blanpain, C. Stem cells: skin regeneration and repair. Nature 464, 686–687 (2010).
Wu, Y., Zhao, R. C. & Tredget, E. E. Concise review: bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration. Stem Cells 28, 905–915 (2010).
Barbosa-Sabanero, K. et al. Lens and retina regeneration: new perspectives from model organisms. Biochem. J. 447, 321–334 (2012).
Gwon, A. Lens regeneration in mammals: a review. Surv. Ophthalmol. 51, 51–62 (2006).
Gwon, A. E., Gruber, L. J. & Mundwiler, K. E. A histologic study of lens regeneration in aphakic rabbits. Invest. Ophthalmol. Vis. Sci. 31, 540–547 (1990).
Cocteau, M. M. & D’Etoille. L. Reproduction du crystallin. J. Physiol. Exp. Pathol. 7, 30–744 (1827).
Henry, J. J. & Hamilton, P. W. Diverse evolutionary origins and mechanisms of lens regeneration. Mol. Biol. Evol. https://doi.org/10.1093/molbev/msy045 (2018).
Beebe, D. C., Feagans, D. E. & Jebens, H. A. Lentropin: a factor in vitreous humor which promotes lens fiber cell differentiation. Proc. Natl Acad. Sci. USA 77, 490–493 (1980).
Lin, H. T. et al. Lens regeneration using endogenous stem cells with gain of visual function. Nature 531, 323–328 (2016).
Kaur, S., Siddiqui, H. & Bhat, M. H. Hepatic progenitor cells in action: liver regeneration or fibrosis? Am. J. Pathol. 185, 2342–2350 (2015).
Chen, J. et al. The diversity and plasticity of adult hepatic progenitor cells and their niche. Liver Int. 37, 1260–1271 (2017).
Heidenreich, P. A. et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ. Heart Fail. 6, 606–619 (2013).
Laflamme, M. A. & Murry, C. E. Heart regeneration. Nature 473, 326–335 (2011).
Senyo, S. E. et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493, 433–436 (2013).
Nakada, Y. et al. Hypoxia induces heart regeneration in adult mice. Nature 541, 222–227 (2017).
Beltrami, A. P. et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114, 763–776 (2003).
Fransioli, J. et al. Evolution of the c-kit-positive cell response to pathological challenge in the myocardium. Stem Cells 26, 1315–1324 (2008).
van Berlo, J. H. et al. c-Kit+cells minimally contribute cardiomyocytes to the heart. Nature 509, 337–341 (2014).
Garbern, J. C. & Lee, R. T. Cardiac stem cell therapy and the promise of heart regeneration. Cell Stem Cell 12, 689–698 (2013).
Schofield, R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 4, 7–25 (1978).
Fuchs, E., Tumbar, T. & Guasch, G. Socializing with the neighbors: stem cells and their niche. Cell 116, 769–778 (2004).
Orford, K. W. & Scadden, D. T. Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation. Nat. Rev. Genet. 9, 115–128 (2008).
Jones, D. L. & Wagers, A. J. No place like home: anatomy and function of the stem cell niche. Nat. Rev. Mol. Cell Biol. 9, 11–21 (2008).
Lander, A. D. et al. What does the concept of the stem cell niche really mean today? BMC Biol. 10, 19 (2012).
Wagers, A. J. The stem cell niche in regenerative medicine. Cell Stem Cell 10, 362–369 (2012).
Watt, F. M. & Fujiwara, H. Cell-extracellular matrix interactions in normal and diseased skin. Cold Spring Harb. Perspect. Biol. 3, a005124 (2011).
Nakayama, K. H., Batchelder, C. A., Lee, C. I. & Tarantal, A. F. Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering. Tissue Eng. Part A 16, 2207–2216 (2010).
Soto-Gutierrez, A. et al. Cell delivery: from cell transplantation to organ engineering. Cell Transplant. 19, 655–665 (2010).
Song, J. J. & Ott, H. C. Organ engineering based on decellularized matrix scaffolds. Trends Mol. Med. 17, 424–432 (2011).
Avigdor, A. et al. CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+stem/progenitor cells to bone marrow. Blood 103, 2981–2989 (2004).
Smith-Berdan, S. et al. Robo4 cooperates with CXCR4 to specify hematopoietic stem cell localization to bone marrow niches. Cell Stem Cell 8, 72–83 (2011).
Morrison, S. J. & Spradling, A. C. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132, 598–611 (2008).
Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).
Flaim, C. J., Chien, S. & Bhatia, S. N. An extracellular matrix microarray for probing cellular differentiation. Nat. Methods 2, 119–125 (2005).
Khetan, S. & Burdick, J. A. Patterning network structure to spatially control cellular remodeling and stem cell fate within 3-dimensional hydrogels. Biomaterials 31, 8228–8234 (2010).
Park, D. et al. Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell 10, 259–272 (2012).
Formiga, F. R. et al. Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration. J. Control. Release 173, 132–139 (2014).
Herberg, S. et al. Development of an injectable composite as a carrier for growth factor-enhanced periodontal regeneration. J. Clin. Periodontol 35, 976–984 (2008).
Erggelet, C. et al. Formation of cartilage repair tissue in articular cartilage defects pretreated with microfracture and covered with cell-free polymer-based implants. J. Orthopaed. Res. 27, 1353–1360 (2009).
Thevenot, P. T. et al. The effect of incorporation of SDF-1 alpha into PLGA scaffolds on stem cell recruitment and the inflammatory response. Biomaterials 31, 3997–4008 (2010).
Mendelson, A., Ahn, J. M., Paluch, K., Embree, M. C. & Mao, J. J. Engineered nasal cartilage by cell homing: a model for augmentative and reconstructive rhinoplasty. Plast. Reconstr. Surg. 133, 1344–1353 (2014).
Dupont, K. M. et al. Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair. Cell Tissue Res. 347, 575–588 (2012).
Lee, C. H. et al. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet 376, 440–448 (2010).
Schantz, J. T., Chim, H. & Whiteman, M. Cell guidance in tissue engineering: SDF-1 mediates site-directed homing of mesenchymal stem cells within three-dimensional polycaprolactone scaffolds. Tissue Engineer. 13, 2615–2624 (2007).
Lee, C. H. et al. Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep. Sci. Transl Med. 6, 266ra171 (2014).
Wang, Y. D., Ameer, G. A., Sheppard, B. J. & Langer, R. A tough biodegradable elastomer. Nat. Biotechnol. 20, 602–606 (2002).
Engelmayr, G. C. et al. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nat. Mater. 7, 1003–1010 (2008).
Chen, Q. Z. et al. An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart. Biomaterials 31, 3885–3893 (2010).
Ravichandran, R., Venugopal, J. R., Sundarrajan, S., Mukherjee, S. & Ramakrishna, S. Cardiogenic differentiation of mesenchymal stem cells on elastomeric poly (glycerol sebacate)/collagen core/shell fibers. World J. Cardiol. 5, 28–41 (2013).
Zaky, S. H. et al. Poly (glycerol sebacate) elastomer supports bone regeneration by its mechanical properties being closer to osteoid tissue rather than to mature bone. Acta Biomater. 54, 95–106 (2017).
Fischer, K. M. et al. Poly(limonene thioether) scaffold for tissue engineering. Adv. Healthc. Mater. 5, 813–821 (2016).
Zhang, L. et al. Zwitterionic hydrogels implanted in mice resist the foreign-body reaction. Nat. Biotechnol. 31, 553–556 (2013).
Bai, T. et al. Restraint of the differentiation of mesenchymal stem cells by a nonfouling zwitterionic hydrogel. Angew. Chem. Int. Ed. 53, 12729–12734 (2014).
Bai, T. et al. Harnessing isomerization-mediated manipulation of nonspecific cell/matrix interactions to reversibly trigger and suspend stem cell differentiation. Chem. Sci. 7, 333–338 (2016).
Malafaya, P. B., Silva, G. A. & Reis, R. L. Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv. Drug Deliv. Rev. 59, 207–233 (2007).
Geesink, R. G. T., Hoefnagels, N. H. & Bulstra, S. K. Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect. J. Bone Joint Surg. Br. 81, 710–718 (1999).
Burkus, J. K., Transfeldt, E. E., Kitchel, S. H., Watkins, R. G. & Balderston, R. A. Clinical and radiographic outcomes of anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2. Spine 27, 2396–2408 (2002).
Nakahara, T. et al. Novel approach to regeneration of periodontal tissues based on in situ tissue engineering: effects of controlled release of basic fibroblast growth factor from a sandwich membrane. Tissue Eng. 9, 153–162 (2003).
van de Kamp, J. et al. Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor-loaded biomaterials. J. Tissue Eng. Regen. Med. 11, 2988–2998 (2017).
Wang, Y. Z., Kim, H. J., Vunjak-Novakovic, G. & Kaplan, D. L. Stem cell-based tissue engineering with silk biomaterials. Biomaterials 27, 6064–6082 (2006).
Ebrahimi, D. et al. Silk-its mysteries, how it is made, and how it is used. ACS Biomater. Sci. Eng. 1, 864–876 (2015).
Li, G. et al. Silk-based biomaterials in biomedical textiles and fiber-based implants. Adv. Healthc. Mater. 4, 1134–1151 (2015).
Dinjaski, N. & Kaplan, D. L. Recombinant protein blends: silk beyond natural design. Curr. Opin. Biotechnol. 39, 1–7 (2016).
Zhang, W. J. et al. VEGF and BMP-2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation. Eur. Cells Mater. 27, 1–12 (2014).
Chen, X. et al. Ligament regeneration using a knitted silk scaffold combined with collagen matrix. Biomaterials 29, 3683–3692 (2008).
Spector, M. Decellularized tissues and organs: an historical perspective and prospects for the future. Biomed. Mater. 11, 020201(2016).
Fu, R. H. et al. Decellularization and recellularization technologies in tissue engineering. Cell Transplant. 23, 621–630 (2014).
Badylak, S. F., Freytes, D. O. & Gilbert, T. W. Extracellular matrix as a biological scaffold material: structure and function. Acta Biomater. 5, 1–13 (2009).
Crapo, P. M., Gilbert, T. W. & Badylak, S. F. An overview of tissue and whole organ decellularization processes. Biomaterials 32, 3233–3243 (2011).
Papadimitropoulos, A., Scotti, C., Bourgine, P., Scherberich, A. & Martin, I. Engineered decellularized matrices to instruct bone regeneration processes. Bone 70, 66–72 (2015).
Martino, M. M., Briquez, P. S., Maruyama, K. & Hubbell, J. A. Extracellular matrix-inspired growth factor delivery systems for bone regeneration. Adv. Drug Deliv. Rev. 94, 41–52 (2015).
Samorezov, J. E. & Alsberg, E. Spatial regulation of controlled bioactive factor delivery for bone tissue engineering. Adv. Drug Deliv. Rev. 84, 45–67 (2015).
Wang, Z. S. et al. The use of platelet-rich fibrin combined with periodontal ligament and jaw bone mesenchymal stem cell sheets for periodontal tissue engineering. Sci. Rep. 6, 28126 (2016).
Ji, B. H. et al. The combination use of platelet-rich fibrin and treated dentin matrix for tooth root regeneration by cell homing. Tissue Eng. Part A 21, 26–34 (2015).
Kim, J. Y. et al. Regeneration of dental-pulp-like tissue by chemotaxis-induced cell homing. Tissue Eng. Part A 16, 3023–3031 (2010).
Jordan, J. E. et al. Bioengineered self-seeding heart valves. J. Thorac. Cardiovasc. Surg. 143, 201–208 (2012).
Place, E. S., Evans, N. D. & Stevens, M. M. Complexity in biomaterials for tissue engineering. Nat. Mater. 8, 457–470 (2009).
Vasita, R., Shanmugam, K. & Katti, D. S. Improved biomaterials for tissue engineering applications: surface modification of polymers. Curr. Top. Med. Chem. 8, 341–353 (2008).
Sionkowska, A. Current research on the blends of natural and synthetic polymers as new biomaterials: review. Prog. Polym. Sci. 36, 1254–1276 (2011).
Doulabi, A. H., Mequanint, K. & Mohammadi, H. Blends and nanocomposite biomaterials for articular cartilage tissue engineering. Materials 7, 5327–5355 (2014).
Zeng, S. et al. Characterization of highly interconnected porous poly(lactic acid) and chitosan-coated poly(lactic acid) scaffold fabricated by vacuum-assisted resin transfer molding and particle leaching. J. Mater. Sci. 51, 9958–9970 (2016).
Salehi, M., Farzamfar, S., Bastami, F. & Tajerian, R. Fabrication and characterization of electrospun PLLA/collagen nanofibrous scaffold coated with chitosan to sustain release of aloe vera gel for skin tissue engineering. Biomed. Eng. Appl. Basis Commun. 28, 1650035 (2016).
Schreinemacher, M. H. F. et al. Degradation of mesh coatings and intraperitoneal adhesion formation in an experimental model. Br. J. Surg. 96, 305–313 (2009).
Chen, M. W., Le, D. Q. S., Kjems, J., Bunger, C. & Lysdahl, H. Improvement of distribution and osteogenic differentiation of human mesenchymal stem cells by hyaluronic acid and beta-tricalcium phosphate-coated polymeric scaffold in vitro. Biores. Open Access 4, 363–373 (2015).
Deepthi, S., Jeevitha, K., Sundaram, M. N., Chennazhi, K. P. & Jayakumar, R. Chitosan-hyaluronic acid hydrogel coated poly(caprolactone) multiscale bilayer scaffold for ligament regeneration. Chem. Engineer. J. 260, 478–485 (2015).
Liao, H. T., Lee, M. Y., Tsai, W. W., Wang, H. C. & Lu, W. C. Osteogenesis of adipose-derived stem cells on polycaprolactone-beta-tricalcium phosphate scaffold fabricated via selective laser sintering and surface coating with collagen type I. J. Tissue Eng. Regen. Med. 10, E337–E353 (2016).
Gottipati, A. & Elder, S. H. Mesenchymal stem cell mediated chondrogenesis on chitosan-calcium phosphate scaffolds: effect of collagen coating. J. Chitin Chitosan Sci. 4, 33–40 (2016).
Takaoka, R., Hikasa, Y. & Tabata, Y. Vascularization around poly(tetrafluoroethylene) mesh with coating of gelatin hydrogel incorporating basic fibroblast growth factor. J. Biomater. Sci. Polym. Ed. 20, 1483–1494 (2009).
Peh, P. et al. Simultaneous delivery of highly diverse bioactive compounds from blend electrospun fibers for skin wound healing. Bioconjug. Chem. 26, 1348–1358 (2015).
Sampaio, S., Miranda, T. M. R., Santos, J. G. & Soares, G. M. B. Preparation of silk fibroin-poly (ethylene glycol) conjugate films through click chemistry. Polymer Int. 60, 1737–1744 (2011).
Ibusuki, S., Fujii, Y., Iwamoto, Y. & Matsuda, T. Tissue-engineered cartilage using an injectable and in situ gelable thermoresponsive gelatin: fabrication and in vitro performance. Tissue Eng. 9, 371–384 (2003).
Cho, J. H. et al. Chondrogenic differentiation of human mesenchymal stem cells using a thermosensitive poly(N-isopropylacrylamide) and water-soluble chitosan copolymer. Biomaterials 25, 5743–5751 (2004).
Burdick, J. A., Mauck, R. L. & Gerecht, S. To serve and protect: hydrogels to improve stem cell-based therapies. Cell Stem Cell 18, 13–15 (2016).
Espinosa-Jeffrey, A. et al. Strategies for endogenous spinal cord repair: HPMA hydrogel to recruit migrating endogenous stem cells. Regen. Biol. Spine Spinal Cord 760, 25–52 (2012).
Wang, Y., Cooke, M. J., Morshead, C. M. & Shoichet, M. S. Hydrogel delivery of erythropoietin to the brain for endogenous stem cell stimulation after stroke injury. Biomaterials 33, 2681–2692 (2012).
Hennink, W. E. & van Nostrum, C. F. Novel crosslinking methods to design hydrogels. Adv. Drug Deliv. Rev. 54, 13–36 (2002).
Tong, X. M. & Yang, F. Sliding hydrogels with mobile molecular ligands and crosslinks as 3D stem cell niche. Adv. Mater. 28, 7257–7263 (2016).
Lin, Y. D. et al. Instructive nanofiber scaffolds with VEGF create a microenvironment for arteriogenesis and cardiac repair. Sci. Transl Med. 4, 146ra109 (2012).
Zhang, Z. P., Hu, J. & Ma, P. X. Nanofiber-based delivery of bioactive agents and stem cells to bone sites. Adv. Drug Deliv. Rev. 64, 1129–1141 (2012).
Xie, J. W. et al. Radially aligned, electrospun nanofibers as dural substitutes for wound closure and tissue regeneration applications. ACS Nano 4, 5027–5036 (2010).
Han, L. H., Yu, S., Wang, T. Y., Behn, A. W. & Yang, F. Microribbon-like elastomers for fabricating macroporous and highly flexible scaffolds that support cell proliferation in 3D. Adv. Funct. Mater. 23, 346–358 (2013).
Raic, A., Rodling, L., Kalbacher, H. & Lee-Thedieck, C. Biomimetic macroporous PEG hydrogels as 3D scaffolds for the multiplication of human hematopoietic stem and progenitor cells. Biomaterials 35, 929–940 (2014).
Murphy, S. V. & Atala, A. 3D bioprinting of tissues and organs. Nat. Biotechnol. 32, 773–785 (2014).
Pati, F., Gantelius, J. & Svahn, H. A. 3D bioprinting of tissue/organ models. Angew. Chem. Int. Ed. 55, 4650–4665 (2016).
Lee, C. H. et al. Three-dimensional printed multiphase scaffolds for regeneration of periodontium complex. Tissue Eng. Part A 20, 1342–1351 (2014).
Abraham, A. C., Edwards, C. R., Odegard, G. M. & Donahue, T. L. H. Regional and fiber orientation dependent shear properties and anisotropy of bovine meniscus. J. Mechan. Behav. Biomed. Mater. 4, 2024–2030 (2011).
Pati, F. et al. Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat. Commun. 5, 3935 (2014).
Miller, J. S. et al. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 11, 768–774 (2012).
Kretlow, J. D., Klouda, L. & Mikos, A. G. Injectable matrices and scaffolds for drug delivery in tissue engineering. Adv. Drug Deliv. Rev. 59, 263–273 (2007).
Seliktar, D. Designing cell-compatible hydrogels for biomedical applications. Science 336, 1124–1128 (2012).
Kim, J. H., Jung, Y., Kim, B. S. & Kim, S. H. Stem cell recruitment and angiogenesis of neuropeptide substance P coupled with self-assembling peptide nanofiber in a mouse hind limb ischemia model. Biomaterials 34, 1657–1668 (2013).
Zhang, Z. P. Injectable biomaterials for stem cell delivery and tissue regeneration. Expert Opin. Biol. Ther. 17, 49–62 (2017).
Douglas, A. M. et al. Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers. Proc. Natl Acad. Sci. USA 114, 885–890 (2017).
Bencherif, S. A. et al. Injectable preformed scaffolds with shape-memory properties. Proc. Natl Acad. Sci. USA 109, 19590–19595 (2012).
Andreas, K., Sittinger, M. & Ringe, J. Toward in situ tissue engineering: chemokine-guided stem cell recruitment. Trends Biotechnol. 32, 483–492 (2014).
Shafiq, M., Jung, Y. & Kim, S. H. In situ vascular regeneration using substance P-immobilised poly (l-lactide-co-epsilon-caprolactone) scaffolds: stem cell recruitment, angiogenesis, and tissue regeneration. Eur. Cell. Mater. 30, 282–302 (2015).
Yamamoto, M., Takahashi, Y. & Tabata, Y. Enhanced bone regeneration at a segmental bone defect by controlled release of bone morphogenetic protein-2 from a biodegradable hydrogel. Tissue Engineer. 12, 1305–1311 (2006).
Osathanon, T. et al. Microporous nanofibrous fibrin-based scaffolds for bone tissue engineering. Biomaterials 29, 4091–4099 (2008).
Salimath, A. S. et al. Dual delivery of hepatocyte and vascular endothelial growth factors via a protease-degradable hydrogel improves cardiac function in rats. PLOS ONE 7, e50980 (2012).
Zhao, J., Zhang, N., Prestwich, G. D. & Wen, X. J. Recruitment of endogenous stem cells for tissue repair. Macromol. Biosci. 8, 836–842 (2008).
Zhang, G. et al. Controlled release of stromal cell-derived factor-1alpha in situ increases C-kit+ cell homing to the infarcted heart. Tissue Eng. 13, 2063–2071 (2007).
Kim, K., Lee, C. H., Kim, B. K. & Mao, J. J. Anatomically shaped tooth and periodontal regeneration by cell homing. J. Dent. Res. 89, 842–847 (2010).
Gao, W. W., Zhang, Y., Zhang, Q. Z. & Zhang, L. F. Nanoparticle-hydrogel: a hybrid biomaterial system for localized drug delivery. Ann. Biomed. Eng. 44, 2049–2061 (2016).
Koehler, K. R., Mikosz, A. M., Molosh, A. I., Patel, D. & Hashino, E. Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature 500, 217–221 (2013).
Benoit, D. S. W., Schwartz, M. P., Durney, A. R. & Anseth, K. S. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat. Mater. 7, 816–823 (2008).
Lin, C. C. & Anseth, K. S. Cell-cell communication mimicry with poly(ethylene glycol) hydrogels for enhancing beta-cell function. Proc. Natl Acad. Sci. USA 108, 6380–6385 (2011).
Zheng, W. T. et al. Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model. Biomaterials 33, 2880–2891 (2012).
Calvert, J. W. et al. Characterization of osteoblast-like behavior of cultured bone marrow stromal cells on various polymer surfaces. J. Biomed. Mater. Res. 52, 279–284 (2000).
Calvert, J. W., Chua, W. C., Gharibjanian, N. A., Dhar, S. & Evans, G. R. D. Osteoblastic phenotype expression of MC3T3-E1 cells cultured on polymer surfaces. Plast. Reconstr. Surg. 116, 567–576 (2005).
Chastain, S. R., Kundu, A. K., Dhar, S., Calvert, J. W. & Putnam, A. J. Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation. J. Biomed. Mater. Res. A 78, 73–85 (2006).
Lee, H., Dellatore, S. M., Miller, W. M. & Messersmith, P. B. Mussel-inspired surface chemistry for multifunctional coatings. Science 318, 426–430 (2007).
Kang, S. M. et al. One-step multipurpose surface functionalization by adhesive catecholamine. Adv. Funct. Mater. 22, 2949–2955 (2012).
Tunuguntla, R. H. et al. Bioelectronic light-gated transistors with biologically tunable performance. Adv. Mater. 27, 831–836 (2015).
Li, W. et al. Microbead-based biomimetic synthetic neighbors enhance survival and function of rat pancreatic beta-cells. Sci. Rep. 3, 2863 (2013).
Hu, C. M. J., Fang, R. H., Copp, J., Luk, B. T. & Zhang, L. A biomimetic nanosponge that absorbs pore-forming toxins. Nat. Nanotechnol. 8, 336–340 (2013).
Hu, C. M. J., Fang, R. H., Luk, B. T. & Zhang, L. Nanoparticle-detained toxins for safe and effective vaccination. Nat. Nanotechnol. 8, 933–938 (2013).
Hu, C.-M. J. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 526, 118–121 (2015).
Chen, W. S. et al. Coating nanofiber scaffolds with beta cell membrane to promote cell proliferation and function. Nanoscale 8, 10364–10370 (2016).
Vining, K. H. & Mooney, D. J. Mechanical forces direct stem cell behaviour in development and regeneration. Nat. Rev. Mol. Cell Biol. 18, 728–742 (2017).
Ladoux, B. & Mege, R.-M. Mechanobiology of collective cell behaviours. Nat. Rev. Mol. Cell Biol. 18, 743–757 (2017).
Li, H., Wijekoon, A. & Leipzig, N. D. 3D differentiation of neural stem cells in macroporous photopolymerizable hydrogel scaffolds. PLOS ONE 7, e48824 (2012).
Vijayavenkataraman, S., Shuo, Z., Fuh, J. Y. H. & Lu, W. F. Design of three-dimensional scaffolds with tunable matrix stiffness for directing stem cell lineage specification: an in silico study. Bioengineering 4, E66 (2017).
Altmann, B. et al. Distinct cell functions of osteoblasts on UV-functionalized titanium- and zirconia-based implant materials are modulated by surface topography. Tissue Eng. Part C Methods 19, 850–863 (2013).
Mozdzen, L. C., Rodgers, R., Banks, J. M., Bailey, R. C. & Harley, B. A. C. Increasing the strength and bioactivity of collagen scaffolds using customizable arrays of 3D-printed polymer fibers. Acta Biomater. 33, 25–33 (2016).
Rujitanaroj, P. O., Wang, Y. C., Wang, J. & Chew, S. Y. Nanofiber-mediated controlled release of siRNA complexes for long term gene-silencing applications. Biomaterials 32, 5915–5923 (2011).
Balmayor, E. R. et al. Modified mRNA for BMP-2 in combination with biomaterials serves as a transcript-activated matrix for effectively inducing osteogenic pathways in stem cells. Stem Cells Dev 26, 25–34 (2017).
Huebsch, N. et al. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation. Nat. Mater. 14, 1269–1277 (2015).
Gardner, R. L. & Johnson, M. H. Investigation of early mammalian development using interspecific chimaeras between rat and mouse. Nat. New Biol. 246, 86–89 (1973).
Rossant, J. & Frels, W. I. Interspecific chimeras in mammals: successful production of live chimeras between Mus musculus and Mus caroli. Science 208, 419–421 (1980).
Fehilly, C. B., Willadsen, S. M. & Tucker, E. M. Interspecific chimaerism between sheep and goat. Nature 307, 634–636 (1984).
Mascetti, V. L. & Pedersen, R. A. Human–mouse chimerism validates human stem cell pluripotency. Cell Stem Cell 18, 67–72 (2016).
Hanna, J. et al. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proc. Natl Acad. Sci. USA 107, 9222–9227 (2010).
Rashid, T., Kobayashi, T. & Nakauchi, H. Revisiting the flight of Icarus: making human organs from PSCs with large animal chimeras. Cell Stem Cell 15, 406–409 (2014).
Wu, J. et al. Interspecies chimerism with mammalian pluripotent stem cells. Cell 168, 473–486 (2017).
National Institutes of Health. NIH research involving introduction of human pluripotent cells into non-human vertebrate animal pre-gastrulation embryos. NIH https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-158.html (2015).
Wu, J. et al. Stem cells and interspecies chimaeras. Nature 540, 51–59 (2016).
National Institutes of Health. Request for public comment on the proposed changes to the NIH guidelines for human stem cell research and the proposed scope of an NIH steering committee’s consideration of certain human–animal chimera research. NIH https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-128.html (2016).
Teixeira, A. I., Duckworth, J. K. & Hermanson, O. Getting the right stuff: controlling neural stem cell state and fate in vivo and in vitro with biomaterials. Cell Res. 17, 56–61 (2007).
Vanden Berg-Foels, W. S. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment. Tissue Eng. Part B Rev. 20, 28–39 (2014).
Huch, M. & Koo, B. K. Modeling mouse and human development using organoid cultures. Development 142, 3113–3125 (2015).
Chen, F. M., Sun, H. H., Lu, H. & Yu, Q. Stem cell-delivery therapeutics for periodontal tissue regeneration. Biomaterials 33, 6320–6344 (2012).
Embree, M. C. et al. Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury. Nat. Commun. 7, 13073 (2016).
Fong, E. L. S., Chan, C. K. & Goodman, S. B. Stem cell homing in musculoskeletal injury. Biomaterials 32, 395–409 (2011).
Avci-Adali, M., Ziemer, G. & Wendel, H. P. Induction of EPC homing on biofunctionalized vascular grafts for rapid in vivo self-endothelialization — a review of current strategies. Biotechnol. Adv. 28, 119–129 (2010).
Cao, Q. L., Benton, R. L. & Whittemore, S. R. Stem cell repair of central nervous system injury. J. Neurosci. Res. 68, 501–510 (2002).
Iwatani, H. & Imai, E. Kidney repair using stem cells: myth or reality as a therapeutic option? J. Nephrol. 23, 143–146 (2010).
Hocking, A. M. & Gibran, N. S. Mesenchymal stem cells: paracrine signaling and differentiation during cutaneous wound repair. Exp. Cell Res. 316, 2213–2219 (2010).
Li, C. Y. et al. Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis. J. Hepatol. 50, 1174–1183 (2009).
Mishra, R., Bishop, T., Valerio, I. L., Fisher, J. P. & Dean, D. The potential impact of bone tissue engineering in the clinic. Regen. Med. 11, 571–587 (2016).
Yu, Y., Wu, R. X., Yin, Y. & Chen, F. M. Directing immunomodulation using biomaterials for endogenous regeneration. J. Mater. Chem. B 4, 569–584 (2016).
Discher, D. E., Mooney, D. J. & Zandstra, P. W. Growth factors, matrices, and forces combine and control stem cells. Science 324, 1673–1677 (2009).
Han, L. H., Tong, X. M. & Yang, F. Photo-crosslinkable PEG-based microribbons for forming 3D macroporous scaffolds with decoupled niche properties. Adv. Mater. 26, 1757–1762 (2014).
Chaudhuri, O. et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat. Mater. 15, 326–334 (2016).
Khetan, S. et al. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat. Mater. 12, 458–465 (2013).
Kragl, M. et al. Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature 460, 60–65 (2009).
Barker, N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat. Rev. Mol. Cell Biol. 15, 19–33 (2014).
Wang, W. E. et al. Dedifferentiation, proliferation, and redifferentiation of adult mammalian cardiomyocytes after ischemic injury. Circulation 136, 834–848 (2017).
Jopling, C. et al. Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464, 606–609 (2010).
Kikuchi, K. et al. Primary contribution to zebrafish heart regeneration by gata4+ cardiomyocytes. Nature 464, 601–605 (2010).
Tornini, V. A. & Poss, K. D. Keeping at arm’s length during regeneration. Dev. Cell 29, 139–145 (2014).
Eguchi, G., Abe, S. I. & Watanabe, K. Differentiation of lens-like structures from newt iris epithelial cells in vitro. Proc. Natl Acad. Sci. USA 71, 5052–5056 (1974).
Takeuchi, J. K. & Bruneau, B. G. Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors. Nature 459, 708–711 (2009).
Godwin, J. The promise of perfect adult tissue repair and regeneration in mammals: learning from regenerative amphibians and fish. Bioessays 36, 861–871 (2014).
Julier, Z., Park, A. J., Briquez, P. S. & Martino, M. M. Promoting tissue regeneration by modulating the immune system. Acta Biomater. 53, 13–28 (2017).
Carrion, F. A. & Figueroa, F. E. Mesenchymal stem cells for the treatment of systemic lupus erythematosus: is the cure for connective tissue diseases within connective tissue? Stem Cell Res. Ther. 2, 23 (2011).
Gattazzo, F., Urciuolo, A. & Bonaldo, P. Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim. Biophys. Acta 1840, 2506–2519 (2014).
Hou, S. et al. The enhancement of cell adherence and inducement of neurite outgrowth of dorsal root ganglia co-cultured with hyaluronic acid hydrogels modified with Nogo-66 receptor antagonist in vitro. Neuroscience 137, 519–529 (2006).
Li, L. C., Ge, J., Wang, L., Guo, B. L. & Ma, P. X. Electroactive nanofibrous biomimetic scaffolds by thermally induced phase separation. J. Mater. Chem. B 2, 6119–6130 (2014).
Dainiak, M. B., Kumar, A., Galaev, I. Y. & Mattiasson, B. Detachment of affinity-captured bioparticles by elastic deformation of a macroporous hydrogel. Proc. Natl Acad. Sci. USA 103, 849–854 (2006).
Kim, J. et al. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat. Biotechnol. 33, 64–72 (2015).
Appel, E. A. et al. Self-assembled hydrogels utilizing polymer-nanoparticle interactions. Nat. Commun. 6, 6295 (2015).
Zhang, Y. et al. Self-assembled colloidal gel using cell membrane-coated nanosponges as building blocks. ACS Nano 11, 11923–11930 (2017).
Naghdi, P. et al. Survival, proliferation and differentiation enhancement of neural stem cells cultured in three-dimensional polyethylene glycol-RGD hydrogel with tenascin. J. Tissue Eng. Regen. Med. 10, 199–208 (2016).
Song, Y. H., Ju, Y., Song, G. B. & Morita, Y. In vitro proliferation and osteogenic differentiation of mesenchymal stem cells on nanoporous alumina. Int. J. Nanomed. 8, 2745–2756 (2013).
Sawyer, A. A., Hennessy, K. M. & Bellis, S. L. The effect of adsorbed serum proteins, RGD and proteoglycan-binding peptides on the adhesion of mesenchymal stem cells to hydroxyapatite. Biomaterials 28, 383–392 (2007).
Qiu, G. et al. Bone regeneration in minipigs via calcium phosphate cement scaffold delivering autologous bone marrow mesenchymal stem cells and platelet-rich plasma. J. Tissue Eng. Regen. Med. 2, e937–e948 (2018).
Kim, T. H., Singh, R. K., Kang, M. S., Kim, J. H. & Kim, H. W. Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration. Nanoscale 8, 8300–8311 (2016).
Quinlan, E. et al. Hypoxia-mimicking bioactive glass/collagen glycosaminoglycan composite scaffolds to enhance angiogenesis and bone repair. Biomaterials 52, 358–366 (2015).
Shih, Y. R. V. et al. Calcium phosphate-bearing matrices induce osteogenic differentiation of stem cells through adenosine signaling. Proc. Natl Acad. Sci. USA 111, 990–995 (2014).
Sun, W. et al. Viability and neuronal differentiation of neural stem cells encapsulated in silk fibroin hydrogel functionalized with an IKVAV peptide. J. Tissue Eng. Regen. Med. 11, 1532–1541 (2017).
Frazier, T. P. et al. Serially transplanted nonpericytic CD146− adipose stromal/stem cells in silk bioscaffolds regenerate adipose tissue in vivo. Stem Cells 34, 1097–1111 (2016).
Sun, J. et al. Controlled release of collagen-binding SDF-1 alpha improves cardiac function after myocardial infarction by recruiting endogenous stem cells. Sci. Rep. 6, 26683 (2016).
Matthias, N. et al. Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with muscle-derived stem cells (MDSCs). Stem Cell Res. 27, 65–73 (2018).
Gaetani, R. et al. Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction. Biomaterials 61, 339–348 (2015).
Simpson, R. M. L. et al. Hyaluronan is crucial for stem cell differentiation into smooth muscle lineage. Stem Cells 34, 1225–1238 (2016).
Deng, B. Y. et al. Delivery of alginate-chitosan hydrogel promotes endogenous repair and preserves cardiac function in rats with myocardial infarction. J. Biomed. Mater. Res. Part A 103, 907–918 (2015).
Tanaka, N., Yamashita, T., Sato, A., Vogel, V. & Tanaka, Y. Simple agarose micro-confinement array and machine-learning-based classification for analyzing the patterned differentiation of mesenchymal stem cells. PLOS ONE 12, e0173647 (2017).
Lal, L., Suraishkumar, G. K. & Nair, P. D. Chitosan-agarose scaffolds supports chondrogenesis of Human Wharton’s Jelly mesenchymal stem cells. J. Biomed. Mater. Res. Part A 105, 1845–1855 (2017).
Canadas, R. F. et al. Polyhydroxyalkanoates: waste glycerol upgrade into electrospun fibrous scaffolds for stem cells culture. Int. J. Biol. Macromol. 71, 131–140 (2014).
Jang, J. et al. 3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair. Biomaterials 112, 264–274 (2017).
Rakian, R. et al. Native extracellular matrix preserves mesenchymal stem cell “stemness” and differentiation potential under serum-free culture conditions. Stem Cell Res. Ther. 6, 235 (2015).
Suzuki, Y. et al. Alginate hydrogel linked with synthetic oligopeptide derived from BMP-2 allows ectopic osteoinduction in vivo. J. Biomed. Mater. Res. 50, 405–409 (2000).
Barnes, B. et al. Lower dose of rhBMP-2 achieves spine fusion when combined with an osteoconductive bulking agent in non-human primates. Spine 30, 1127–1133 (2005).
Haidar, Z. S., Hamdy, R. C. & Tabrizian, M. Biocompatibility and safety of a hybrid core-shell nanoparticulate OP-1 delivery system intramuscularly administered in rats. Biomaterials 31, 2746–2754 (2010).
Woo, B. H., Jiang, G., Jo, Y. W. & DeLuca, P. P. Preparation and characterization of a composite PLGA and poly(acryloyl hydroxyethyl starch) microsphere system for protein delivery. Pharm. Res. 18, 1600–1606 (2001).
Woodruff, M. A. et al. Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model. J. Mol. Histol. 38, 425–433 (2007).
Mabilleau, G. et al. Effects of FGF-2 release from a hydrogel polymer on bone mass and microarchitecture. Biomaterials 29, 1593–1600 (2008).
Lim, T. C. et al. Chemotactic recruitment of adult neural progenitor cells into multifunctional hydrogels providing sustained SDF-1 alpha release and compatible structural support. FASEB J. 27, 1023–1033 (2013).
Erggelet, C. et al. Regeneration of ovine articular cartilage defects by cell-free polymer-based implants. Biomaterials 28, 5570–5580 (2007).
De Visscher, G., Mesure, L., Meuris, B., Ivanova, A. & Flameng, W. Improved endothelialization and reduced thrombosis by coating a synthetic vascular graft with fibronectin and stem cell homing factor SDF-1 alpha. Acta Biomater. 8, 1330–1338 (2012).
Kuwabara, F. et al. Novel small-caliber vascular grafts with trimeric peptide for acceleration of endothelialization. Ann. Thorac. Surg. 93, 156–163 (2012).
Borselli, C. et al. Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc. Natl Acad. Sci. USA 107, 3287–3292 (2010).
Abbushi, A. et al. Regeneration of intervertebral disc tissue by resorbable cell-free polyglycolic acid-based implants in a rabbit model of disc degeneration. Spine 33, 1527–1532 (2008).
Acknowledgements
The authors thank the members of the laboratories of H.X., L.Z. and K.Z. for helpful discussions. This study was funded by the National Natural Science Foundation of China (Grant Nos 81771629, 81770510, 81671498 and 81600399).
Author information
Authors and Affiliations
Contributions
H.X., L.Z. and K.Z. designed the study. All authors discussed the results and wrote and commented on the manuscript.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Related links
CC-BY-NC-ND-4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/
Organ Procurement and Transplantation Network: https://www.organdonor.gov/statistics-stories/statistics.html
Rights and permissions
About this article
Cite this article
Xia, H., Li, X., Gao, W. et al. Tissue repair and regeneration with endogenous stem cells. Nat Rev Mater 3, 174–193 (2018). https://doi.org/10.1038/s41578-018-0027-6
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41578-018-0027-6