This study discusses how diabetic neuropathy (DN) frequently leads to foot ulcers and ultimately limb amputations without effective clinical therapy. DN is characterized by reduced vascularity in the peripheral nerves and deficiency in angiogenic and neurotrophic factors. Only delivering neurotrophic or angiogenic factors for treatment in the form of protein or gene therapy is very modest if not ineffective.

Mesenchymal stem cells (MSCs) have been highlighted as a new emerging regenerative therapy owing to their multipotency for DN.  MSCs reverse manifestations of DN, repair tissue, and antihyperglycemia. MSCs also paracrinely secrete neurotrophic factors, angiogenic factors, cytokines, and immunomodulatory substances to ameliorate DN.

Challenges in the clinical translation of MSC therapy include safety, optimal dose of administration, optimal mode of cell delivery, issues of MSC heterogeneity, clinically meaningful engraftment, autologous or allogeneic approach, challenges with cell manufacture, and further mechanisms.

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