Mesenchymal Stem Cell-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Ameliorate Diabetic Polyneuropathy in Mice

Abstract

Background. Although pathological involvements of diabetic polyneuropathy (DPN) have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs) ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs) into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN. Research Design and Methods. For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated. Results. The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100β in the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice. Conclusions. These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.

hiPSC‐derived iMSCs: NextGen MSCs as an advanced therapeutically active cell resource for regenerative medicine

“…Himeno et al . have demonstrated that iMSCs from mice exhibited characteristic mice MSC surface marker such as CD105, CD140a, Sca‐1 and CD44 as previously described . The immunosuppressive, cytoprotection and tissue regeneration properties are exerted by the paracrine factors secreted by the MSCs .…”

Wound repair and regeneration: Mechanisms, signaling, and translation

“…More recently, revertant keratinocytes of a junctional epidermolysis bullosa patient with compound heterozygous COL17A1 mutations used an iPSC approach to generate genetically corrected keratinocytes (155). In addition, iPSCs have been shown to ameliorate diabetic polyneuropathy (a neuropathic disorder associated with diabetes mellitus) in mice (156), and to activate an angiogenic response in mice with hindlimb ischemia (157). …”

Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds

“…53 The transplanted cells in hindlimb muscles and peripheral nerves of mouse model for diabetic polyneuropathy (DPN), ameliorated nerve conduction velocities, plantar skin blood flow, increased the number-to-muscle fiber ratios, suggesting that iPS-MSC transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells. 54 Moreover, recent studies have further support the use of iPS in skin regeneration. The authors successfully used human keratinocyte-derived iPSCs to reconstitute skin in vitro for the treatment of recessive dystrophic epidermolysis bullosa.…”