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Table 2 Characteristics of the MSC-based therapies in T2DM

From: Applicability of adipose-derived mesenchymal stem cells in treatment of patients with type 2 diabetes

Stem cell type With control study Number of patients Sex male/female Mean age (years) Mean history of disease (years) Mean dose of injected cells Mode of injection Mean follow-up period Glycometabolic control β cell function Insulin sensitivity Immunological recovery Complications Author
BM-MNCs 25 17/8 55.8 13.2 Intra-pancreatic 12 months 4/15 insulin-free, 13/15 reduced insulin requirements ≥ 50%, HbA1C decreased 29.5% C-Pep improved No adverse effects Estrada et al. [43]
BM-MNCs Yes Ctrl 20
MNCs 20
11/9
12/8
54.9
56.4
9.5
9.8
MNC 4.0 × 109 Intra-pancreatic 12 months Insulin dose decreased 30%, HbA1C decreased 13% in the treated group FCP improved Transient abdominal pain
Punctual hemorrhage
Wu et al. [44]
BM-MNCs 10 8/2 57.5 14.6 MNC 3.5 × 108
(CD34+  3.1 × 106)
Intra-pancreatic 6 months 3/10 insulin-free, 7/10 reduced insulin requirements ≥ 50%, HbA1C decreased 13.1% FCP, glucagon-stimulated C-Pep improved, HOMA-β increased HOMA-IR no change Hematoma
Hemoglobin
Respiratory infection
Bhansali et al. [45]
BM-MNCs 31 MNC 3.76 × 109 Intra-pancreatic 24 months 7/26 reduced insulin requirements, HbA1C decreased 18.4% C-Pep improved Wang et al. [46]
BM-MNCs Yes Ctrl 62
MNCs 56
36/18
38/18
50.2
50.4
7.3
8.6
MNC 2.8 × 109 Intra-pancreatic 33 months 18/56 insulin-free, 37/56 reduced insulin requirements ≥ 50%,
HbA1C decreased 13.1% in treated group;
Insulin dose increased gradually in control
FCP, PCP improved in treated group; decreased in control No adverse effects Hu et al. [47]
BM-MNCs
+P-MNCs
Yes Ctrl 10
MNCs 11
7/3
9/2
54
51
20
12
MNC 2.9 × 108
(CD34+ 3.2 × 106)
P-MNC 4.9 × 108
(CD34+ 5.8 × 106)
Twice treatment
Intra-pancreatic
IV
12 months 9/11 reduced insulin requirements ≥ 50%, 10/11 maintain HbA1c < 7% in treated group Glucagon-stimulated C-Pep improved in treated group, HOMA-β no difference HOMA-IR lower in treated group Punctual related effects Bhansali et al. [48]
BM-MNCs/MSCs Yes Ctrl 10
MNCs 10
MSCs 10
6/4
7/3
8/2
53.5
44.5
50.5
14
13
15
MNC 1.1 × 109
(CD34+ 1.8 × 107)
MSC 8.35 × 107
Intra-pancreatic 12 months 6/10 reduced insulin requirements ≥ 50%, maintain HbA1c < 7% in both treated groups;
None improved in the control group
Glucagon-stimulated C-Pep improved in the MNC group ISI improved in MSCs group Punctual hemorrhage
Hypoglycemic
Bhansali et al. [49]
WJ-MSCs 22 15/7 52.9 8.7 1 × 106/kg Twice treatment
IV
Intra-pancreatic
12 months 7/17 insulin-free, 12/17 reduced insulin requirements ≥ 50%
HbA1C decreased 15%
FCP improved; HOMA-β increased T lymphocytes decreased, IL-6 and IL-1β reduced Punctual hemorrhage
Fever
C-pep temporary decreased
Liu et al. [50]
WJ-MSCs 6 6/0 40.5 3.6 0.88 × 106/kg
0.87 × 106/kg
Twice treatment
IV
24 months 3/6 insulin-free, FCP, PCP improved No adverse effects Guan et al. [51]
WJ-MSCs Yes Ctrl 30
MSC 31
16/14
17/14
53.2
52.4
8.3
8.93
1.0 × 106/kg Twice treatment
IV
36 months 10/31 insulin-free, 18/31 reduced insulin requirements ≥ 50%,
HbA1C decreased 25.8% in treated group;
Insulin dose increased gradually in control
FCP improved;
HOMA-β increased
HOMA-IR decreased trend Hypoglycemia Hu et al. [52]
UC-MSCs 18 1 × 106/kg Thrice treatment
IV
6 months Insulin requirements without reduced C-Pep without improved Tregs increased trend Fever Kong et al. [53]
PD-MSCs 10 7/3 66 11 1.35 × 106/kg Thrice treatment
IV
6 months 4/10 reduced insulin requirements ≥ 50%,
HbA1C decreased 31.6%
C-Pep improved No adverse effects Jiang et al. [54]
CB-SCs 36 21/15 52 14 Stem cell educator therapy 14 months Insulin dose, oral medications, HbA1C decreased FCP improved; HOMA-β increased HOMA-IR reduced TGF-β1, CTLA-4 increased; IL-17, IL-12,IL-4, IL-5,CD86 + CD14+ monocytes decreased;
increased
Punctual-related effects Zhao et al. [55]
  1. Abbreviations: MNCs mononuclear stem cells, MSCs mesenchymal stem cells, BM bone marrow, P peripheral, WJ Wharton’s jelly, UC umbilical cord, PD placenta-derived, CB-SC cord blood-derived multipotent stem cells, Ctrl control, IV intravenous, FCP fasting c-peptide, PCP postprandial c-peptide, C-Pep c-peptide, HOMA-β homeostatic model assessment of beta cell function, HOMA-IR homeostasis model assessment of insulin resistance, ISI insulin sensitivity index