Nature Outlook |
Our bodies aren’t forever: parts wear out, trauma breaks things and organs stop functioning. Sometimes, a drug can remedy a chemical imbalance or surgery can repair a structural failure, but there are times when there is no substitute for replacing a part with human tissue or even an entire organ. Rapid advances in the field of regenerative medicine are bringing that possibility closer to reality.
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For centuries, scientists have been captivated by the phenomenal feats of regeneration found in nature. Despite decades of research, attempts to replace or repair parts of the human body have met with only modest success. Fresh understanding of organ formation coupled with new technologies may help to unlock long-sought cures.
Stem-cell therapy promises to restore motor function after a stroke or spinal-cord injury, but neurologists are proceeding with caution.
Advances in technology have outpaced our understanding of organ development and injury response. It's time to reassess, says Stephen Badylak.
Machines that deposit cell-laden inks are constructing tissues and organs, one layer at a time.
Some animals can regrow body parts with ease. Biologists hope to figure out their secrets and apply them to humans.
Cell therapy could cure type 1 diabetes — if only the immune system didn't get in the way.
Adult stem cells have become a regulatory battleground as clinicians, scientists and ethicists debate whether the road to the clinic should be shorter.
The regenerative properties of muscle stem cells decline with age, as they enter an irreversible senescence state. Pura Muñoz-Cánoves and colleagues show that before entering senescence, mouse muscle stem cells preserve their repair properties by returning to a reversible quiescence state in an autophagy-dependent manner. Preventing autophagy in young satellite stem cells promotes their entry into senescence and correlates with an increase in mitochondrial dysfunction and oxidative stress. Conversely, promoting autophagy in old satellite cells reverses senescence and restores their regenerative properties in an injury model.
Ken Poss and colleagues identify an injury-dependent enhancer element that activates gene expression in regenerating zebrafish tissues. They find that the element, which they term a 'tissue regeneration enhancer element' (TREE), is divisible into tissue-specific modules that can each direct expression in zebrafish hearts or fins. The identified element can be used to direct the expression of pro- or anti-regenerative factors in zebrafish tissues and thus control the efficiency of regeneration. Finally, by engineering TREEs upstream of mitogenic factor genes, the authors demonstrate their ability to boost tissue repair in injured mouse tissue.
Grafting of caudalized rodent or human neural progenitor cells into sites of spinal cord injury enables true regeneration of damaged corticospinal axons in rodents. Regenerating axons form functional synapses within the graft, can extend beyond the lesion site, and help to support functional motor recovery.
Resection of the diseased gastrointestinal tract can lead to surgical complications and low quality of life. In this Review, Bitar summarizes advances in gastrointestinal tissue engineering and regenerative medicine that aim to overcome these complications and restore tissue function.
The clinical translation of biomaterials for tissue engineering reveals their therapeutic performance and relevance, and thus enables the improvement of biomaterials design. In this Review, the design and translation of biomaterials, particularly cartilage and cornea repair, and a new understanding of the interaction between biomaterials and the host immune system are discussed.
Some features of salamander limb regeneration following amputation have puzzled developmental biologists for years. Although experimental grafting shows that juxtaposition of anterior and posterior limb, as well as innervation, are sufficient to induce the formation of a limb, the mechanism involved has been a mystery. Elly Tanaka and colleagues have now identified fibroblast growth factor 8 (FGF8) as a key anterior signal, acting in concert with posteriorly localized sonic hedgehog (SHH) signalling to drive non-regenerating tissue into forming a full limb.
Strategies for inducing immunological tolerance to transplanted cells are an important component of regenerative therapies.
In this Perspective, the authors discuss the importance of intrinsic and extrinsic factors in muscle regeneration, and they conclude that both are necessary for the action of muscle stem cells in the aging process.
It is widely believed that the astrocytic scars that develop following central nervous system (CNS) injury are a major obstacle to subsequent axonal regrowth. But here Michael Sofroniew and colleagues demonstrate that limiting the formation of the scar actually attenuates axon re-growth. Sustained delivery of axon-specific growth factors not typically present in spinal cord lesions allowed for robust re-growth, but only if the astrocytic scar was present. These results question the prevailing dogma and suggest that astrocyte scarring promotes — rather than prevents — CNS axon regeneration post-injury.
An acellular biologic scaffold treatment for volumetric muscle loss: results of a 13-patient cohort study
People who have lost muscle could regain some muscle mass, movement and strength by implanting non-cellular supportive material from pig tissue. Jenna Dziki, Stephen Badylak, J. Peter Rubin and other colleagues from the University of Pittsburgh in the United States implanted extracellular matrix–the material secreted by cells to support surrounding tissue–derived from the urinary bladder, small intestine and skin of pigs at the sites of muscle tissue loss in 13 patients, followed by aggressive physiotherapy. Six months after surgery, the team observed an average improvement of 37% in muscle strength, 27% in range of motion tasks, and a 20% or greater improvement in at least one functional task. They found that the implanted supportive matrix degraded, promoted stem cell mobilization and new muscle formation, with an average increase in muscle mass of 27% and improved nerve supply to the area. The results pave the way for new treatments for muscle loss due to tumor removal, accidents or disease.