Abstract
Current cell-based therapies to treat degenerative diseases such as osteoarthritis (OA) fail to offer long-term beneficial effects. The therapeutic effects provided by mesenchymal stem cell (MSC) injection, characterized by reduced pain and an improved functional activity in patients with knee OA, are reported at short-term follow-up since the improved outcomes plateau or, even worse, decline several months after MSC administration. This review tackles the limitations of MSC-based therapy for degenerative diseases and highlights the lessons learned from regenerative species to comprehend the coordination of molecular and cellular events critical for complex regeneration processes. We discuss how MSC injection generates a positive cascade of events resulting in a long-lasting systemic immune regulation with limited beneficial effects on tissue regeneration while in regenerative species fine-tuned inflammation is required for progenitor cell proliferation, differentiation, and regeneration. Finally, we stress the direct or indirect involvement of neural crest derived cells (NCC) in most if not all adult regenerative models studied so far. This review underlines the regenerative potential of NCC and the limitations of MSC-based therapy to open new avenues for the treatment of degenerative diseases such as OA.
Highlights
Epimorphic regeneration is a process allowing some vertebrates to regrow complete functional appendages after previous amputation
We have shown the crucial role of TNFa/TNFR1 axis mediated by macrophages during caudal fin regeneration, which induces blastema proliferation (Nguyen-Chi et al, 2017)
This review underlines how the well-recognized heterogeneity of mesenchymal stem cell (MSC) has greatly contributed to limit their success in degenerative disease therapies
Summary
Epimorphic regeneration is a process allowing some vertebrates to regrow complete functional appendages after previous amputation. Adult mammals are not able to regenerate their limbs after injury. Few vertebrates such as anurans can regenerate their tissues during early development before their metamorphosis and others such as teleost can regrow appendages throughout life. The teleost group presents many specimens able to regenerate. The zebrafish, Danio rerio, is able to regenerate their fins throughout its life, and is a relevant model at adult and larva stages to study this process (White et al, 1994; Marques et al, 2019). Young humans and adult mice present regenerative abilities after digit tip amputation (Choi et al, 2014)
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