Mesenchymal stem cells in ischemic tissue regeneration

Table 1 Minimal criteria for defining mesenchymal stem cells

Morphology, growth conditions	Spindle-shaped (fibroblast-like), adherent
Specific surface markers	CD73+, CD90+, CD105+, CD11b-, CD14-, CD19-, CD45-, CD79α-, MHC-II, HLA-DR-
Differentiation potential	Adipogenic, chondrogenic, osteogenic

HLA: Human leukocyte antigen; MHC: Major histocompatibility complex.

Table 2 Selected clinical trials of mesenchymal stem cell-based therapy in ischemic diseases

Disorder	Ref.	Trial number (acronym)	Type of transplant and stem cell source	Results
Myocardial infarction	Hare et al[36], 2009	NCT00114452	Allogenic BM-MSCs	No tumorogenicity, no arrythomogenicity
Myocardial infarction	Houtgraaf et al[37], 2012	NCT00442806 (APOLLO)	Autologous AT-MSCs	No adverse effects, decreased: Scar tissue; increased: Perfusion
Myocardial infarction	Gao et al[122], 2015	NCT01291329	Allogenic WJ-MSCs	Increased: Ejection fraction; decreased: Heart perfusion
Chronic ischemic cardiomyopathy	Hare et al[123], 2012	NCT01087996 (POSEIDON)	Allogenic vs autologous BM-MSCs	Increased: Ejection fraction; decreased: Scar tissue
Chronic ischemic cardiomyopathy	Karantalis et al[124], 2014	NCT00587990 (PROMETHEUS)	Autologous BM-MSCs	Local; increased: Contraction; decreased: Scar tissue
Chronic ischemic cardiomyopathy	Perin et al[125], 2014	NCT00426868 (PRECISE)	Autologous AT-MSCs	Increased: Left ventricular mass; increased: Contractility; increased: Perfusion
Chronic ischemic cardiomyopathy	Bartunek et al[126], 2013	NCT00810238 (C-CURE)	Preconditioned autologous BM-MSCs	Increased: Ejection fraction
Chronic ischemic cardiomyopathy	Bartolucci et al[118], 2017	NCT01739777 (RIMECARD)	Allogenic UC-MSCs	Increased: Ejection fraction
Ischemic heart failure	Teerlink et al[127], 2017	NCT01768702 (CHART-1)	Autologous BM-MSCs	Left ventricular reverse remodelling, increased: Left ventricular volume
Critical limb ischemia	Wijnand et al[128], 2018	NCT03042572 (SAIL)	Allogenic BM-MSCs	Safety, decreased: Pain rest
Critical limb ischemia	Norgren et al[129], 2018	NCT01732822 (EUCLID)	Allogeneic placental-derived MSCs	Increased: Amputation-free survival; decreased: Pain rest; increased: Tissue perfusion
Critical limb ischemia	Gupta et al[130], 2013	NCT00883870	Allogenic BM-MSCs	Decreased: Pain rest; increased: Ankle systolic pressure; increased: Ulcer healing
Ischemic stroke	Steinberg et al[131], 2016	NCT01287936	Modified BM-MSCs	Increased: Motor functions (ESS, NIHSS, Fugle-Meyer scales)
Ischemic stroke	Levy et al[132], 2019	NCT01297413	Allogenic BM-MSCs	Increased: Barthel index
Ischemic stroke	Savitz et al[133], 2019	NCT01273337 (RECOVER-Stroke)	Autologous BM-MSCs	Safety
Ischemic stroke	Laskowitz et al[134], 2018	NCT03004976	Allogenic UCB-MSCs	Safety and feasibility
Ischemic stroke	Jaillard et al[135], 2020	NCT00875654	Autologous BM-MSCs	Increased: Motor functions (NIHSS, Fugle-Meyer scales)

BM: Bone marrow; AT: Adipose tissue; WJ: Wharton’s jelly; UC: Umbilical cord; MSCs: Mesenchymal stem cells; ESS: European Stroke Scale; NIHSS: National Institutes of Health Stroke Scale.