Low back pain is a very common symptom in people all over the world, which is now the leading cause of disability worldwide1,2. Although the specific cause of low back pain is rarely determined, lumbar intervertebral disc degeneration is considered to be the main cause of low back pain3. So far, neither conservative treatment nor surgical treatment can prevent or at least slow down the degenerative process4,5. For this reason, regenerative medicine, the repair of degenerate discs by intradiscal injection of exogenous cells, is emerging as a promising approach4. However, due to its distinctive structure and function, disc presents unique characteristics: largely avascular, hypoxia, low pH, high osmotic pressure and high mechanical load4,6,7. This situation establishes an adverse microenvironment for resident cells and delivered exogenous cells, which limits the effect of cell therapy4,5. In addition, there are still other considerable challenges in the entire translational spectrum of cell therapy, including the lack of guidelines for disease classification and patient stratification, as well as a marked lack of understanding of the characteristics of neural distribution, cell fate, and long-term prospects for disc regeneration in the context of cell therapy. In this comment, we will discuss the key issues mentioned above in disc cell therapy.
Intervertebral disc degeneration and cell therapy
The intervertebral disc is a complex cartilage structure whose function is to resist biomechanical loading during spinal movement. It is composed of a highly viscous nucleus pulposus surrounded by a thick fibrocartilage outer ring, annulus fibrosus, and sandwiched by cartilage endplates below and above (Fig. 1a). Intervertebral disc cells actively regulate their metabolic activities in a paracrine and/or autocrine manner through a variety of substances, including cytokines, enzymes, enzyme inhibitors, and growth factors. The degeneration of the intervertebral disc is characterized by a decrease in the number of viable cells, especially the number of nucleus pulposus cells, and the decline of their function, resulting in the loss of extracellular matrix (ECM), especially proteoglycans8. As the disc degenerates and becomes more dehydrated, the lamellar structure of the annulus fibrosus becomes disorganized and the disc loses its structural integrity9. Cartilage endplates tend to calcify, reducing nutrient delivery to cells9. With inflammation, blood vessels, and nerves may grow into the inner layer of the annulus fibrosus and nucleus pulposus (Fig. 1b), which correlate to the low back pain7,10. These pathophysiological changes will lead to the loss of mechanical tension of the annulus fibrosus and the pressure of the intervertebral disc. Therefore, the ability to maintain or reconstitute ECM by increasing the number of viable cells in the degenerate disc and altering the balance between synthesis and degradation is an emerging therapeutic strategy5. At the same time, cell therapy can alleviate the pain of disc origin through immune regulation and inhibition of inflammation8,11.
Cell therapy for disc degeneration involves the delivery of viable cells to the nucleus pulposus12,13,14 (Fig. 1b), annulus fibrosus15,16 or systemic application17,18, either alone or in combination with biomaterial scaffolds and carriers5, making it possible to repopulate and repair degenerate discs, or at least modulate the degenerate microenvironment8. Various cell types, such as intervertebral disc-derived cells19,20,21,22,23,24,25,26, chondrocyte-like cells27,28, mesenchymal stromal cells (MSCs)13,29,30,31,32,33,34,35, olfactory36, embryonic37, hematopoietic38, or induced pluripotent39,40,41 stem cells have been used for regenerative therapy of degenerate discs in basic and/or clinical studies (Table 1). Among these cells, MSCs represent a particularly attractive option and have been widely used in regenerative medicine owing to their easy preparation, self-renewal ability, multilineage differentiation potential, and anti-inflammatory and immunosuppressive properties8. This proof of concept has been confirmed by a large number of preclinical studies and several early clinical trials, which provide encouraging results in regenerative effect and reducing low back pain, respectively42.
Which patients are suitable for cell therapy?
One of the most difficult questions yet to be answered is related to patient selection8,9. Which patients are most suitable for cell therapy? When considering the clinical success of cell therapy, it is very important to determine the status of intervertebral disc and evaluate the applicability of cell therapy. Patients come to the clinician because of back pain, not because they are worried about disc degeneration9. In fact, many patients with severe disc degeneration have no symptoms. Therefore, back pain rather than disc degeneration should be a clinical goal. In most cases, it is not known whether low back pain is caused by intervertebral disc. Other structures, such as facet joints and sacroiliac joints, may also be involved, so even if the degenerate disc is completely regenerated, the pain may not be cured9.
Magnetic resonance imaging (MRI) can well reveal the degeneration and degree of disc degeneration, but it cannot distinguish which degenerative disc is a painful disc5. With the increase of age, the loss of proteoglycans in intervertebral disc gradually increases. Therefore, ~10% of intervertebral disc at the age of 50 and ~60% of intervertebral disc at the age of 70 degenerate seriously43. This leaves a basic question, that is, what is symptomatic pathology and what is only age-related disc degeneration. Provocative discography now is a diagnostic option. With the emergence of intervertebral disc regenerative medicine, lumbar discography is more and more widely used in pre-injection planning12,32,44. However, lumbar discography has been discredited and may indeed cause further disc degeneration45. Thus, there is no reliable method to determine which disc is the source of pain. It is urgent to develop new tools to diagnose painful discs requiring cell therapy5. New, advanced imaging tools for this purpose are currently under development, including MRI techniques such as T1ρ and T2 relaxation times, as well as chemical exchange saturation transfer, and quantification of circulating biomarkers4.
Can cell therapy eliminate nociceptive nerve fibers?
An increase in innervation is associated with pain of disc origin46. The mechanism of nerve growth and hyperinnervation of pathologically painful disc has not been fully clarified. The molecules that may be involved in this process are some members of the neurotrophin (NTs) family, especially nerve growth factor (NGF), which is known to have neurotrophic and neurotropic properties and regulate the density and distribution of nerve fibers in degenerate disc. NGF and its receptors are expressed in healthy intervertebral discs, but higher levels are observed in painful discs, indicating a correlation between the expression level of NGF and the innervation density of intervertebral discs46,47. In addition, anti-NGF therapy has been shown to induce analgesia and show efficacy in patients with chronic low back pain48.
A major disadvantage is that no studies to date have been conducted to address the effects of MSCs delivered to the painful disc on ectopic sensory nerve distribution characteristics. Few studies have evaluated the interaction between the delivered cells and the native disc microenvironment, especially with regard to the innervated disc. Strong evidence supports the anti-inflammatory effect of delivery cells in the degenerate discs8. However, more and more other applied studies have shown that the regenerative ability of MSCs in neurological diseases, and the NGF and its receptors released by MSCs can enhance nerve survival and neurite outgrowth49,50,51,52. Therefore, delivery of MSCs to patients with innervated discs may aggravate pain symptoms by supporting the ingrowth of these nociceptive fibers. So far, in the published clinical trials of disc cell therapy, there is always a group of ineffective patients; However, it is unclear why these patients did not show any improvement in pain and disability scores. One possible cause of persistent pain in patients with innervated disc is the survival and migration of neural network mediated by stem cells after delivery53.
Can the delivered exogenous cells survive within degenerate disc?
The nutrient supply of the intervertebral disc cells is mainly through the cartilage endplate. As the intervertebral disc degenerates, endplate calcification may occur and inhibit the diffusion of solutes from the sub-endplate capillary network to the intervertebral disc. In degenerate discs, this nutritional route is hindered, affecting the activity and survival of the implanted cells9,11. A large number of animal studies and limited human studies have found that cells remain survive weeks and months after cell transplantation, but few studies have explored longer-term results54,55. However, disc repair is a very lengthy process. Type II collagen from healthy mature individuals has a long turnover time, on the order of hundreds of years. This means that the ability of the transplanted cells to produce and secrete the correct matrix components is insufficient for long-term function, as the biomechanically indispensable architectural structures are difficult to form56.
Cell therapy that significantly increases the anabolic activity of cells in the degenerate disc and thus increases the nutrient demand will over imbalance the nutritional environment, resulting in cell death or decreased cell activity. Therefore, cell therapy is likely to reduce rather than enhance the activity and viability of delivered cells. Blindly pursuing the intervertebral disc repair strategy to promote cell proliferation and anabolic activity without considering the nutritional environment in the degenerate disc may not be the correct direction of intervertebral disc regeneration. Considering the reduced availability of nutrients during disc degeneration and the importance of adequate nutrition for cell survival, this effect should be considered first when designing disc regeneration strategies5,11. Although, more recently, the silicon model study of the in vivo nutrient microenvironment of degenerative intervertebral disc has been found nutrient concentrations may increase by a reduction in diffusional distance due to reduced disc height and vasculature ingrowth57. Furthermore, 2-D steady state finite element mathematical modeling research also demonstrated distinct disc morphologies has an important influence on the diffusion gradient of intervertebral disc and found the effect of transplanted cells on nutrition may be limited, with some considerations on dosage58. However, the main limitation of these studies is the pure diffusion hypothesis, which still needs to be confirmed by further research. In addition, cell therapy can also produce various angiogenic factors, including vascular endothelial growth factor and fibroblastic growth factor, to promote angiogenesis, which is also essential for the disc repair8,53.
Can cell therapy regenerate degenerate discs?
Mechanical loading of the disc initiates cell-mediated remodeling events that lead to disc degeneration59,60. A large number of animal models use altered biomechanics to induce disc degeneration61. These models show that although the disc is intact, over time, the altered biomechanical loading can lead to catabolic cell responses and remodeling of the disc matrix. In vitro studies showed that moderate cyclic loading had anabolic effect on disc cells, while static overloading showed catabolic effect62. High tension strain applied to human disc cells in vitro has been shown to drive cytokines and inflammatory responses related to intervertebral disc degeneration63. Therefore, the relationship between mechanical loading and cell function is considered to be a key component of intervertebral disc function and dysfunction.
The interaction of cells, ECM and biomechanical stress contributes to the homeostasis of the intervertebral disc. If the disc cells do not receive the appropriate mechanical signals, they will stop production and even begin to degrade proteoglycans. The reduction of proteoglycans will cause the pressure in the intervertebral disc to drop, which will change the biomechanical pressure of the cells. Therefore, the positive feedback loop of intervertebral disc degeneration can be deduced, which includes the degenerative cycle of cells, ECM and biomechanics64.
Intervertebral disc degeneration is always accompanied by a decrease in pressure within the disc and abnormal load distribution. Under these mechanical conditions, cell therapy to regenerate degenerate discs is almost impossible. From a biomechanical point of view, disc regeneration may only occur under conditions of restoration of pressure and load distribution within the disc. Dynamic stabilization systems now offer the potential for mechanical approaches to disc regeneration. Dynamic stabilization systems using pedicle screws or interspinous devices have shown restabilization of spinal segments and reduction of intradiscal pressure61. Numerous clinical studies have shown that degenerative discs receiving dynamic stabilization systems lead to disc regeneration65. Combining disc cell-based therapy with a dynamic stabilization system may be the future development direction for the treatment of intervertebral disc degeneration.
Conclusions
Although cell-based therapy for disc degeneration has made considerable progress, there are still quite a few hurdles to overcome. In this comment, we present major concerns and possible solutions in cell therapy for disc degeneration (Table 2). Further research is needed to develop new tools for diagnosing painful discs that require cell therapy, to develop alternative pathways to eliminate nociceptors growing in painful discs, to further understand the fate and action mechanism of transplanted cells, and to restore the mechanical environment of degenerate discs, so that cell therapy finally moves from the laboratory to the clinic.
Reporting summary
Further information on research design is available in the Nature Research Reporting Summary linked to this article.
Data availability
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
References
Knezevic, N. N., Candido, K. D., Vlaeyen, J. W. S., Van Zundert, J. & Cohen, S. P. Low back pain. Lancet 398, 78–92 (2021).
Vlaeyen, J. W. S. et al. Low back pain. Nat. Rev. Dis. Prim. 4, 52 (2018).
Lyu, F. J. et al. Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions. Bone Res. 9, 7 (2021).
Smith, L. J. et al. Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section. JOR Spine 1, e1036 (2018).
Sakai, D. & Andersson, G. B. Stem cell therapy for intervertebral disc regeneration: obstacles and solutions. Nat. Rev. Rheumatol. 11, 243–256 (2015).
Loibl, M. et al. Controversies in regenerative medicine: should intervertebral disc degeneration be treated with mesenchymal stem cells? JOR Spine 2, e1043 (2019).
Fournier, D. E., Kiser, P. K., Shoemaker, J. K., Battie, M. C. & Seguin, C. A. Vascularization of the human intervertebral disc: a scoping review. JOR Spine 3, e1123 (2020).
Binch, A. L. A., Fitzgerald, J. C., Growney, E. A. & Barry, F. Cell-based strategies for IVD repair: clinical progress and translational obstacles. Nat. Rev. Rheumatol. 17, 158–175 (2021).
Bendtsen, M. et al. Biological challenges for regeneration of the degenerated disc using cellular therapies. Acta Orthop. 87, 39–46 (2016).
Groh, A. M. R., Fournier, D. E., Battie, M. C. & Seguin, C. A. Innervation of the human intervertebral disc: a scoping review. Pain. Med 22, 1281–1304 (2021).
Huang, Y. C., Urban, J. P. & Luk, K. D. Intervertebral disc regeneration: do nutrients lead the way? Nat. Rev. Rheumatol. 10, 561–566 (2014).
Elabd, C. et al. Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study. J. Transl. Med. 14, 253 (2016).
Noriega, D. C. et al. Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation 101, 1945–1951 (2017).
Amirdelfan, K. et al. Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease: a prospective randomized, placebo-controlled 36-month study of safety and efficacy. Spine J. 21, 212–230 (2021).
Nukaga, T., Sakai, D., Schol, J., Sato, M. & Watanabe, M. Annulus fibrosus cell sheets limit disc degeneration in a rat annulus fibrosus injury model. JOR Spine 2, e1050 (2019).
Pirvu, T. et al. A combined biomaterial and cellular approach for annulus fibrosus rupture repair. Biomaterials 42, 11–19 (2015).
Wang, P. et al. Effects and safety of allogenic mesenchymal stem cell intravenous infusion in active ankylosing spondylitis patients who failed NSAIDs: a 20-week clinical trial. Cell Transpl. 23, 1293–1303 (2014).
Tam, V., Rogers, I., Chan, D., Leung, V. Y. & Cheung, K. M. A comparison of intravenous and intradiscal delivery of multipotential stem cells on the healing of injured intervertebral disk. J. Orthop. Res. 32, 819–825 (2014).
Bach, F. C. et al. Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside. Oncotarget 9, 26507–26526 (2018).
Sato, M. et al. An experimental study of the regeneration of the intervertebral disc with an allograft of cultured annulus fibrosus cells using a tissue-engineering method. Spine 28, 548–553 (2003).
Ganey, T. et al. Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine 28, 2609–2620 (2003).
Meisel, H. J. et al. Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol. Eng. 24, 5–21 (2007).
Tschugg, A. et al. A prospective randomized multicenter phase I/II clinical trial to evaluate safety and efficacy of NOVOCART disk plus autologous disk chondrocyte transplantation in the treatment of nucleotomized and degenerative lumbar disks to avoid secondary disease: safety results of Phase I-a short report. Neurosurg. Rev. 40, 155–162 (2017).
Richardson, S. M. et al. Notochordal and nucleus pulposus marker expression is maintained by sub-populations of adult human nucleus pulposus cells through aging and degeneration. Sci. Rep. 7, 1501 (2017).
Huang, B., Zhuang, Y., Li, C. Q., Liu, L. T. & Zhou, Y. Regeneration of the intervertebral disc with nucleus pulposus cell-seeded collagen II/hyaluronan/chondroitin-6-sulfate tri-copolymer constructs in a rabbit disc degeneration model. Spine 36, 2252–2259 (2011).
Iwashina, T. et al. Feasibility of using a human nucleus pulposus cell line as a cell source in cell transplantation therapy for intervertebral disc degeneration. Spine 31, 1177–1186 (2006).
Gorensek, M. et al. Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. Cell Mol. Biol. Lett. 9, 363–373 (2004).
Acosta, F. L. Jr. et al. Porcine intervertebral disc repair using allogeneic juvenile articular chondrocytes or mesenchymal stem cells. Tissue Eng. A 17, 3045–3055 (2011).
Miyamoto, T. et al. Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits. Arthritis Res. Ther. 12, R206 (2010).
Wang, F. et al. Injectable hydrogel combined with nucleus pulposus-derived mesenchymal stem cells for the treatment of degenerative intervertebral disc in rats. Stem Cells Int. 2019, 8496025 (2019).
Hoogendoorn, R. J. et al. Adipose stem cells for intervertebral disc regeneration: current status and concepts for the future. J. Cell Mol. Med. 12, 2205–2216 (2008).
Kumar, H. et al. Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study. Stem Cell Res. Ther. 8, 262 (2017).
Pang, X., Yang, H. & Peng, B. Human umbilical cord mesenchymal stem cell transplantation for the treatment of chronic discogenic low back pain. Pain. Physician 17, E525–E530 (2014).
Leckie, S. K. et al. Injection of human umbilical tissue-derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo. Spine J. 13, 263–272 (2013).
Blanco, J. F. et al. Autologous mesenchymal stromal cells embedded in tricalcium phosphate for posterolateral spinal fusion: results of a prospective phase I/II clinical trial with long-term follow-up. Stem Cell Res. Ther. 10, 63 (2019).
Murrell, W., Sanford, E., Anderberg, L., Cavanagh, B. & Mackay-Sim, A. Olfactory stem cells can be induced to express chondrogenic phenotype in a rat intervertebral disc injury model. Spine J. 9, 585–594 (2009).
Sheikh, H. et al. In vivo intervertebral disc regeneration using stem cell-derived chondroprogenitors. J. Neurosurg. Spine 10, 265–272 (2009).
Haufe, S. M. & Mork, A. R. Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev. 15, 136–137 (2006).
Zhu, Y. et al. The generation and functional characterization of induced pluripotent stem cells from human intervertebral disc nucleus pulposus cells. Oncotarget 8, 42700–42711 (2017).
Sheyn, D. et al. Human iPSCs can be differentiated into notochordal cells that reduce intervertebral disc degeneration in a porcine model. Theranostics 9, 7506–7524 (2019).
Xia, K. et al. Intradiscal injection of induced pluripotent stem cell-derived nucleus pulposus-like cell-seeded polymeric microspheres promotes rat disc regeneration. Stem Cells Int. 2019, 6806540 (2019).
Vadala, G., Ambrosio, L., Russo, F., Papalia, R. & Denaro, V. Stem cells and intervertebral disc regeneration overview-what they can and can’t do. Int. J. Spine Surg. 15, 40–53 (2021).
van Uden, S., Silva-Correia, J., Oliveira, J. M. & Reis, R. L. Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities. Biomater. Res. 21, 22 (2017).
Orozco, L. et al. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 92, 822–828 (2011).
Cuellar, J. M. et al. Does provocative discography cause clinically important injury to the lumbar intervertebral disc? A 10-year matched cohort study. Spine J. 16, 273–280 (2016).
Garcia-Cosamalon, J. et al. Intervertebral disc, sensory nerves and neurotrophins: who is who in discogenic pain? J. Anat. 217, 1–15 (2010).
Risbud, M. V. & Shapiro, I. M. Role of cytokines in intervertebral disc degeneration: pain and disc content. Nat. Rev. Rheumatol. 10, 44–56 (2014).
Schmelz, M. et al. Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety. Pain 160, 2210–2220 (2019).
Zha, K. et al. Nerve growth factor (NGF) and NGF receptors in mesenchymal stem/stromal cells: Impact on potential therapies. Stem Cells Transl. Med. 10, 1008–1020 (2021).
Crigler, L., Robey, R. C., Asawachaicharn, A., Gaupp, D. & Phinney, D. G. Human mesenchymal stem cell subpopulations express a variety of neuro-regulatory molecules and promote neuronal cell survival and neuritogenesis. Exp. Neurol. 198, 54–64 (2006).
Peng, J. et al. Human umbilical cord Wharton’s jelly-derived mesenchymal stem cells differentiate into a Schwann-cell phenotype and promote neurite outgrowth in vitro. Brain Res. Bull. 84, 235–243 (2011).
Rbia, N. et al. Seeding decellularized nerve allografts with adipose-derived mesenchymal stromal cells: An in vitro analysis of the gene expression and growth factors produced. J. Plast. Reconstr. Aesthet. Surg. 72, 1316–1325 (2019).
Binch, A. L. A., Richardson, S. M., Hoyland, J. A. & Barry, F. P. Combinatorial conditioning of adipose derived-mesenchymal stem cells enhances their neurovascular potential: Implications for intervertebral disc degeneration. JOR Spine 2, e1072 (2019).
Williams, R. J., Tryfonidou, M. A., Snuggs, J. W. & Le Maitre, C. L. Cell sources proposed for nucleus pulposus regeneration. JOR Spine 4, e1175 (2021).
Henriksson, H. B. et al. The traceability of mesenchymal stromal cells after injection into degenerated discs in patients with low back pain. Stem Cells Dev. 28, 1203–1211 (2019).
Malda, J., Groll, J. & van Weeren, P. R. Rethinking articular cartilage regeneration based on a 250-year-old statement. Nat. Rev. Rheumatol. 15, 571–572 (2019).
McDonnell, E. E. & Buckley, C. T. Consolidating and re-evaluating the human disc nutrient microenvironment. JOR Spine 5, e1192 (2022).
Shalash, W., Ahrens, S. R., Bardonova, L. A., Byvaltsev, V. A. & Giers, M. B. Patient-specific apparent diffusion maps used to model nutrient availability in degenerated intervertebral discs. JOR Spine 4, e1179 (2021).
Setton, L. A. & Chen, J. Mechanobiology of the intervertebral disc and relevance to disc degeneration. J. Bone Joint Surg. Am. 88, 52–55 (2006).
Fearing, B. V., Hernandez, P. A., Setton, L. A. & Chahine, N. O. Mechanotransduction and cell biomechanics of the intervertebral disc. JOR Spine 1, e1026 (2018).
Schnake, K. J., Putzier, M., Haas, N. P. & Kandziora, F. Mechanical concepts for disc regeneration. Eur. Spine J. 15, S354–S360 (2006).
Wang, D. L., Jiang, S. D. & Dai, L. Y. Biologic response of the intervertebral disc to static and dynamic compression in vitro. Spine 32, 2521–2528 (2007).
Ashinsky, B., Smith, H. E., Mauck, R. L. & Gullbrand, S. E. Intervertebral disc degeneration and regeneration: a motion segment perspective. Eur. Cell Mater. 41, 370–380 (2021).
Vergroesen, P. P. et al. Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthritis Cartilage 23, 1057–1070 (2015).
Yilmaz, A. et al. Disc rehydration after dynamic stabilization: a report of 59 cases. Asian Spine J. 11, 348–355 (2017).
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Peng, B., Li, Y. Concerns about cell therapy for intervertebral disc degeneration. npj Regen Med 7, 46 (2022). https://doi.org/10.1038/s41536-022-00245-4
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DOI: https://doi.org/10.1038/s41536-022-00245-4
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