Autologous and allogeneic mesenchymal stem cell-based therapies for diabetes mellitus: A systematic review and meta-analysis

Table 1 Glycemic outcomes in each of the studies that are chosen for assessing eligibility for meta-analysis

Ref.	Type of study							HbA1c	FBG	C-peptide levels	PBG	Insulin requirements
	Randomized	Non-randomized	Blindness	Prospective	Retrospective	Parallel	Cross over
Cai et al[12]1	+		NB	+		+		+	+	+		+
Packham et al[13]1	+		DB	+		+		+
Carlsson et al[14]1	+		NB	+		+		+		+		+
Leão et al[15]1		+	NB		+	+		+
Skyler et al[16]1	+		SB	+		+			+	+
Thakkar et al[17]1		+	NB	+		+		+	+	+	+	+
Zhao et al[18]1	+		NB	+		+		+		+
Wu et al[19]1	+		NB	+		+		+	+	+		+
Wu et al[20]1	+		NB	+		+		+	+	+		+
Vanikar et al[21]2		+	NB	+		+		+	+	+	+	+
Bhansali et al[22]2	+		SB	+		+		+	+	+		+
Hu et al[23]2	+		SB	+		+		+	+	+		+
Hu et al[24]2	+		DB	+		+		+	+	+	+	+
Jiang et al[25]2		+	NB	+				+	+	+		+
Li et al[26]2		+	NB	+				+	+	+	+	+
Lian et al[27]2		+	NB	+				+	+	+	+	+
Liu et al[28]2		+	NB	+		+		+	+	+	+	+
Moon et al[29]2	+		SB	+		+		+	+		+
Nguyen et al[30]2	+		NB	+		+		+	+	+		+
De Guzman et al[31]2		+	NB	+				+	+			+
Guan et al[32]2		+	NB	+				+	+	+
Purwati et al[33]2		+	NB	+				+	+	+		+

¹Studies that have undergone meta-analysis.

²Studies that have not undergone meta-analysis.

HbA1c: Hemoglobin A1c; FBG: Fasting blood glucose; PBG: Postprandial blood glucose; DB: Double blind; NB: Not blinded; SB: Single blinded.

Table 2 Detailed information about the characteristics of mesenchymal stem cells that are used in studies that underwent meta-analysis, and the various methods by which mesenchymal stem cells are grafted

Ref.	Source of MSCs	Type of graft of MSCs	Type of grafting method of MSCs	Targeted tissue/organ
Cai et al[12]	UC-MSCs and aBM-MNCs	Allogeneic	Intra-arterial infusion via supra-selective pancreatic artery cannulation	Pancreas
Packham et al[13]	BM-MPCs	Allogeneic	IV infusion	Kidneys
Carlsson et al[14]	BM-MSCs	Autologous	IV infusion	Pancreas
Leão et al[15]	ASCs	Allogeneic	IV infusion	Systemic administration
Skyler et al[16]	BM-MPCs	Allogeneic	IV infusion	Systemic administration
Thakkar et al[17]	IS-AD-MSCs and BM-HSCs	Autologous	Infusion into the portal vein, thymic circulation, and subcutaneous tissue	Pancreas and subcutaneous tissue
Zhao et al[18]	CB-SCs	Allogeneic	Stem cell educator therapy	Pancreas
			Re-infusion of educated lymphocytes into the patient’s circulation
Wu et al[19]	BM-MNCs	Autologous	Pancreatic intra-arterial infusion via the dorsal pancreatic artery	Pancreas
Wu et al[20]	BM-MSCs	Autologous	Intra-arterial and intravenous infusion	Pancreas

MSC: Mesenchymal stem cell; UC-MSCs: Umbilical cord-derived mesenchymal stem cells; aBM-MNCs: Autologous bone marrow mononuclear cells; BM-MPCs: Bone marrow-derived mesenchymal progenitor cells; BM-MSCs: Bone marrow-derived mesenchymal stem cells; ASCs: Adipose-derived mesenchymal stem cells; BM-MPCs: Bone marrow-derived mesenchymal progenitor cells; IV: Intravenous; IS-AD-MSCs: Adipose tissue derived insulin-secreting mesenchymal stem cells; BM-HSCs: Bone marrow-derived hematopoietic stem cells; CB-SCs: Cord-blood-derived multipotent stem cells; BM-MNCs: Bone marrow mononuclear cells.

Table 3 The reasons for the usage of different sources for extracting mesenchymal stromal cells in order to treat diabetes mellitus[45]

MSC source	Proliferation rate	Immunomodulation	Angiogenesis	Differentiation potential	Clinical applications in diabetes
BM-MSCs	Moderate	Strong	Moderate	Osteogenic, adipogenic, chondrogenic	Immune modulation, islet transplantation support
AD-MSCs	High	Strong	High	Adipogenic, osteogenic, chondrogenic	Insulin sensitivity, wound healing
UC-MSCs	Very high	Strongest	High	Osteogenic, chondrogenic, myogenic	Autoimmune diabetes (T1DM), regenerative therapy
WJ-MSCs	Very high	Strongest	High	Osteogenic, chondrogenic, myogenic	β-cell protection, allogeneic therapy
PD-MSCs	High	Strong	Very high	Multipotent	β-cell protection, neuroprotection, tissue repair

MSC: Mesenchymal stem cell; BM-MSCs: Bone marrow-derived mesenchymal stem cells; AD-MSCs: Adipose tissue derived mesenchymal stem cells; UC-MSCs: Umbilical cord-derived mesenchymal stem cells; T1DM: Type 1 diabetes mellitus; WJ-MSCs: Wharton’s jelly mesenchymal stem cells; PD-MSCs: Pluripotent-derived mesenchymal stem cells.