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.

当前用于治疗退化性疾病如骨关节炎（OA）的基于细胞的疗法未能提供长期的有益效果。在短期随访中报告了间充质干细胞（MSC）注射提供的治疗效果，其特点是减轻了疼痛并改善了膝OA患者的功能活动，因为结局平稳期改善了，甚至更糟的是下降了几个月在MSC管理之后。这篇综述解决了基于MSC的退行性疾病治疗的局限性，并着重指出了从再生物种中学到的教训，以理解对于复杂的再生过程至关重要的分子和细胞事件的协调。我们讨论了MSC注射如何产生积极的事件级联反应，从而导致持久的全身免疫调节，对组织再生的有益作用有限，而在再生物种中，祖细胞的增殖，分化和再生需要微调的炎症。最后，我们强调到目前为止研究的大多数（如果不是全部）成人再生模型都直接或间接涉及神经（衍生细胞（NCC）。这项审查强调了NCC的再生潜力和基于MSC的治疗方法的局限性，为治疗诸如OA等退行性疾病开辟了新途径。我们强调到目前为止，即使不是全部研究的大多数成人再生模型，神经neural衍生细胞（NCC）都直接或间接参与。这项审查强调了NCC的再生潜力和基于MSC的治疗方法的局限性，为治疗诸如OA等退行性疾病开辟了新途径。我们强调到目前为止，即使不是全部研究的大多数成人再生模型，神经neural衍生细胞（NCC）都直接或间接参与。这项审查强调了NCC的再生潜力和基于MSC的治疗方法的局限性，为治疗诸如OA等退行性疾病开辟了新途径。