Table 2.
Stem cells enhance angiogenesis and wound healing in DFUs. Neonatal porcine bone marrow-derived mesenchymal stem cell (npBM-MSC), Adipose-derived mesenchymal stem cells (ADSCs), human induced pluripotent stem cell-derived smooth muscle cells (hiPSCSMC), endothelial differentiated adipose-derived stem cells (EC-ADSCs), human umbilical cord blood-derived CD34+ stem cells (UCB-CD34+SC), bone marrow mononuclear cells (BMMNCs), endothelial progenitor cells, human fetal aorta-derived CD133+ progenitor cells and their conditioned medium (CD133+ CCM), human umbilical cord-derived MSCs (hucMSCs).
| Stem Cell | Strategy | Parameters Checked | Outcome |
|---|---|---|---|
| npBM-MSC [29] | Xenotransplantation in mice model of diabetic wound. |
Rate of wound closure and the promotion of neovascularization | The wound closure rate was significantly improved on postoperative days 4 and 7 Promoted angiogenesis and lymphangiogenesis |
| ADSCs [30] | Autologous transplantation in mice | Lymphangiogenesis Wound healing |
ADSCs accelerate lymphatic endothelial cells proliferation, migration, and lymphangiogenesis ADSCs enhance VEGFR3-mediated lymphangiogenesis via METTL3-mediated VEGF-C m6A modification to improve wound healing in DFUs |
| hiPSCSMC [31] |
Xenotransplantation hiPSC-SMC embedded in 3D collagen scaffolds were applied to diabetic, nude mice with splinted back wounds | To compare angiogenic factor secretion from ADMCs and hiPSCSMC | hiPSC-SMC secretes increased concentration of pro-angiogenic cytokines compared with murine ADMCs. hiPSC-SMC-containing collagen scaffolds accelerate diabetic wound healing hiPSC-SMC increases the number of total and M2 macrophages hiPSC-SMC increases angiogenesis via VEGF-A and TGF-β1 |
| ADSCs [32] | Autologous transplantation in swine | Percentage of wound healing | Increased percentage of wound closure rates with ADSCs and EC-ADSCs, and conditioned media Increased angiogenesis with stem cell therapy Significant decrease in inflammation with stem cells |
| hUCB-CD34+SC [33] |
Xenotransplantation in a rat model of diabetic wound locally. |
To evaluate the efficacy of stem cells in the healing of wounds | A significant decrease in mean wound surface area, increase in mean epidermal thickness, blood vessel proliferation, and collagen deposition |
| EPCs-BMMNCs | Autologous stem cells transplantation in mice topically | Wound healing and angiogenesis | Accelerated wound healing and induced expression of VEGF and bFGF promoting angiogenesis |
| CD133+ CCM [34] | Xenotransplantation in mice model of diabetic wound |
Wound healing and angiogenesis | Stimulation of migration, angiogenesis-like network formation and induction of Wnt expression Stimulate wound healing by paracrine mechanisms |
| ABCB5+MSCs [35] |
Human dermal ABCB5+ MSCs were transplanted via intramuscular injection in mice ischemic limb and topically in human DFUs | To evaluate the angiogenic potential of ABCB5+ MSCs |
In mice Accelerated perfusion recovery of ischemia Increased angiogenesis Clinical trial in human Reduction in wound surface area in therapy refractory DFUs with topical application |
| hucMSCs [36] | hucMSCs were infused in diabetic rat | Repair of diabetic vascular endothelial cell damage | hucMSCs ameliorated blood glucose and protected vascular endothelium from diabetic damage through paracrine effect involving MAPK/ERK signaling |