Progress and expectation of stem cell therapy for diabetic wound healing

Table 1 Recent clinical trials regarding stem cell therapies for diabetic wounds

Ref.	Type of stem cells	Number of cases	Mean age (year)	Methods of treatment	Possible mechanism	Outcome	Adverse events	Conciusion
Uzun et al[49], 2021	ADMSCs	10	57.5	Intralesional injection	The release of angiogenic cytokines, increasing epithelialization, granulation tissue formation, anti-inflammatory, and anti-apoptotic effects	Time to wound closure (d): ADMSCs group (n = 10): 31.0 ± 10.7; Control group (n = 10): 54.8 ± 15.0; P = 0.002	No found	Allogeneic ADMSCs injection is a safe and effective method with a positive contribution to wound-healing time in the treatment of chronic diabetic foot ulcers
Suzdaltseva et al[51], 2020	UCMSCs	31	58.5	Intralesional injection	The release of angiogenic cytokines, cell differentiation, and immunomodulation	Complete wound closure or significant improvement (% in group)a: UCMSCs group (n = 59): 22%; Placebo group (n = 49): 8.2%; P < 0.05	No found	Locally delivered allogeneic UCMSCs can contribute to chronic wound repair and provide an additional support toward new therapeutic strategies
Moon et al[50], 2019	ADMSCs	30	59.9	Topical	Synthesizing higher amounts of collagen, fibroblast growth factor, and vascular endothelial growth factor in vitro	Complete wound closure at Week 12 (% in group): ADMSCs group (n = 30): 82%; Control group (n = 29): 53%; P < 0.05	No found	Allogeneic ADMSCs might be effective and safe to treat diabetic foot ulcers
Chen et al[53], 2018	BMMSCs	1	64	Intramuscular injection	The release of angiogenic cytokines, differentiation and angiogen	No recurrence in the next 10-yr follow-up span	No found	Autologous BMMSC transplantation therapy may be an effective measure for recurrent bullosis diabeticorum
Qin et al[52], 2016	UCMSCs	28	75	Intravascular and intralesional injection	The release of signalling or growth factors, and differentiation of injected precursor cells into functional tissue	Increased number of vessels: Experimental group (n = 28): 9.3 ± 2.7; Control group (n = 25): 5.9 ± 3.3; P < 0.05	No found	UCMSC transplantation after angioplasty is a safe and effective clinical therapy for severe diabetic foot
Xu et al[55], 2016	Peripheral blood stem cells	63	69	Intralesional injection	Angiogenesis and vascularization	CTA scoreb: Pre-transplantation (n = 63): 1.22 ± 0.15; Post-transplantation (n = 63): 2.35 ± 0.784; P < 0.01	No found	Autologous peripheral blood stem cell transplantation can promote the establishment of collateral circulation in patients with diabetic foot
Lu et al[54], 2011	BMMSCs	18	63	Intramuscular injection	The release of angiogenic cytokines, differentiation and angiogenesis	Angiographic score of MRA in limbs at 24 wkb: BMMSCs (n = 18): 1.9 ± 0.5; BMMNCs (n = 19): 1.5 ± 0.6; P = 0.018	No found	BMMSCs therapy may be better tolerated and more effective than BMMNCs for increasing lower limb perfusion and promoting foot ulcer healing in diabetic patients with critical limb ischemia

^a108 patients, including 31 patients (28.7%) suffering from diabetic foot, were randomized to the umbilical cord mesenchymal stromal cell group and placebo group.

^b0 points, no new collateral vessels; 1 point, little new collateral circulation; 2 points, moderate new collateral circulation; 3 points, abundant new collateral circulation.

ADMSCs: Adipose-derived mesenchymal stromal cells; UCMSCs: Umbilical cord mesenchymal stromal cells; BMMSCs: Bone marrow mesenchymal stem cells; CTA: Computed tomography angiography; MRA: Magnetic resonance angiography; BMMNCs: Bone marrow-derived mononuclear cells.