Pickup and drop-off included
T2DM156 (T), 62 (C)18-60 y (T=8.6 ± 6.5, C=7.3 ± 6.3)
1-2-3 mo, every 3 mo until -36 mo
T: Auto BM-MNC Dose ? DPA, 1xC: ( – )
T: D, E, PST, BGM-MAC: D, E, PST, IIT, BGM-MA
HbA1c and C peptide in treatment were significantly better than either pre-therapy values or control.In Treatment:18/56 patients insulin was discontinued;19/56 insulin reduction > 50%, 10/56 insulin reduction 15-50%, 9/56 –non responderIn control: 40/62 patients – insulin requirement increased > 50%, 22/62 patients – increased 15-45%.
T2DM20 (MNC-HBO), 20 (MNC), 20 (C1=HBO), 20 (C2)40-65 y (2 – 15 y)
3-6-9-12 mo
Auto BM-MNCT1: MNC-HBO= 3641.2 ± 1585.4 MT2: MNC= 4012.5 ± 1431.9MDPA – 10 minutes 1x
T and C: D, L, PST, SBGM- IA
Insulin dose reduction at 12 mo in T1 and T2, C1, C2 – unchangedInsulin free: T1: 1/20, T2: 2/20Improvement at 12 mo in AUC C-Pep of T1= T2 > C1, and AUC Ins of T1 and T2.HbA1c at 3, 6, 9 and 12 mo -reduced significantly both in T1 and T2, but stable in C1 and C2.FBG at 6, 9 and 12 months – T1 and T2 -reduced Fasting C peptide at 3, 6, 9 and 12 mo significantly elevated in T1 and T2, but remained stable in C1 and C2
T2DM11 (T), 10 (C)T=46.5–56 y (10-15.5 y)C= 52.5–56 y (16-21 y)
2-4-6-8-10- 12wk-4-5-6- 9-12 mo
T: auto BM- MNC – 290 M (220 -380 M)C: sham, saline SP/DA -1x after 12 wk:PB- GCSF- leucopheresis MNC – 490 (290–730M)C: sham, saline –IV-1x
T and C: D, L, E, W-SBGM – IA
12 mo: 50% Insulin reduction-Tr: 9/11 = 82%, -C:0/10, p= 0.002Insulin red Tr > C (p=0.001, 6 mo), (p=0.004, 12 mo)HbA1C maintenance (
<7%): Tr 10/11 (91%), C 6/10 (60%), p= 0.167
Increase in glucagon stimulated C peptide: Tr > C, p= 0.036
Correlation insulin decrease-C peptide increase r= 0.8, p=0.01)
T2DM10 (MSC), 10 (MNC), 10 (C)MSC= 36-58 (8-23) MNC= 39.5-50 (8.5-15) C= 43-59 (9-15)
2-4-8-12- wk-6-9-12 mo
AutoBM-MSC-P4-5 – 1M/ kg BWAuto BM-MNC – 1B/patient C= vit. B complex SPDA – 1x
T and C: L, PST,D-SBGM- IA
6/10 (MSC), 6/10 (MNC), 0/10 (C) achieved primary end point: 50% insulin requirement reduction, while maintaining HbA1c
<7.0% -> significant difference
MNC group: Increase in glucagon stimulated C peptide
MSC group: Improvement in insulin sensitivity index and increase in IRS-1 gene expression
T2DM31 (T), 30(C) 18-60 y(T=8.93±5.67 C=8.3±6.07)
36 mo
T: Wharton jelly MSC P41M/kg BWC: SalineIV – 2x (interval 4 wk)
T and C: D, E, PST, SBGM- MA
Blood glucose, HbA1c, Cpeptide, homeostasis model assessment of pancreatic islet cell function signifi- cantly improved- compared to control.
Incidence of diabetic complications: Tr – no increase vs baseline, C: 4/30- new diabetic retinopathy, 3/30 new diabetic neuropathy 3/30 new diabetic nephropathy –> statistically significant difference (Tr vs C, P= 0.007)
Insulin dose reduction:Tr: 18/31- 50% insulin dose reduction ( where 10/31 – insulin free from 311 mo postWJMSC, and insulin free duration 12.5±6.8 months), 5/31 -1550% reduction, and 8/31 non responder. Control: 14/30: >50% insulin dose increase, 16/30: 1545% insulin dose increase – 30/30 – non responder
T2DM + impotence2 7 (T), 3 (C)57-87 (12-52 y, impo- tence minimal 6 months)
2wk – 11 mo
T: UCB SC -His tos- tem, ABO, HLA- ABC, DR, and sex- matched – 15MC: saline Injection – CC -1x
T and C:PST, D-SBGM-MA
Tr: Blood glucose levels decreased by 2 weeks, and medication dosages were reduced for 4 to 7 months (6/7). HbA1c levels improved after treatment for up to 3 to 4 months (7/7)Reduced insulin dose after 1 month (2/7)Control: no improvement in blood glucose level, HbA1c, and insulin dose.
T2DM 315 (T1), 15 (T2), 15 (T3), 3×5 C)T1= 57.7±8.2y (10.8± 7.3y )T2= 55.3±11.4y (10.2± 5.7y)T3= 57.2 ±6.6y (9.6±4.5y)C= 58.7 ±7.3y (9.8±6.7y)
12 wk 2y post study
MPC- P(?) Rexleme- strocel-L – mesoblas Inc, cryo-thawedT1=0.3 M/kg T2=1 M/kg T3=2 M/kg C= placebo IV- 45 minutes 1X
T and C: L, PST, BGM-RT
Tr: HbA1c – reduced – at all time points after week 1, C: a small increase in HbA1cClinical target HbA1c
<7% was achieved by 0/15 of Control, 2/15 of T1, 1/15 of T2, and 5/15 of T3 (P < 0.05)
Glycemic rescue therapy was required by: 1/15 of Con- trol, 2/15 of T1, 0/15 of T2, 1/15 of T3.
T2DM413 (T), 13 (C) 10-58 y (0.5 – 11 y)
1y
Hu fetal liver HSC – 35-55 M (20% CD34)- cryo-thawedSaline (C) IV – 1x
T and C: BGM-FU
Up to 1 y, no significant improvement in fasting blood glucose, and C peptide compared to control.Improvement in – HbA1c only at 6th mo: 7.9±1.3 in treatment vs 7.0 ± 0.86 in control (p=0.046).None of the treatment become insulin free.
Current Stem Cell Research & Therapy, 2018(13)"Towards Standardized Stem Cell Therapy in Type 2 Diabetes Mellitus: A Systematic Review"Jeanne Adiwinata Pawitan, Zheng Yang, Ying Nan Wu, and Eng Hin Lee
[20] Hu J, Li C, Wang L, et al. Long-term effects of autologous bone marrow mononuclear cell implantation for type 2 diabetes mellitus. Endocr J 2012; 59(11): 1031-9.
[21] Wu Z, Cai J, Chen J, et al. Autologous bone marrow mononuclear cell infusion and hyperbaric oxygen therapy in type 2 diabetes mellitus: an open-label, randomized controlled clinical trial. Cytotherapy 2014; 16: 258-65.
[22] Bhansali A, Asokumar P, Walia R, et al. Efficacy and safety of autologous bone marrow-derived stem cell transplantation in type 2 diabetes mellitus patients: a randomized placebo-controlled study. Cell Transplant 2014; 23(9): 1075-85.
[23] Bhansali A, Upreti V, Khandelwal N, et al. Efficacy of autologous bone marrow-derived stem cell transplantation in type 2 diabetes mellitus patients. Stem Cells Dev 2009; 18(10): 1407-16.
[24] Hu J, Wang Y, Gong H, et al. Long-term effects and safety of Wharton's jelly-derived mesenchymal stem cells in type 2 diabetes. Experimental and Therapeutic Medicine 2016; 12(3): 1857-66.
[25] Bahk JY, Jung JH, Han H, Min SK, Lee YS. Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant 2010; 8(2): 150-60.
[26] Skyler JS, Fonseca VA, Segal KR, et al. Allogeneic mesenchymal precursor cells in type 2 diabetes: A randomized, placebo-controlled, dose-escalation safety and tolerability pilot study. Diabetes Care 2015; 38(9): 1742-9.
[27] Ghodsi M, Heshmat R, Amoli M, et al. The effect of fetal liver-derived cell suspension allotransplantation on diabetic patients: first year of follow-up. Acta Med Iran 2012; 50(8): 541-6.
20
T2DM156 (T), 62 (C)18-60 y (T=8.6 ± 6.5, C=7.3 ± 6.3)
1-2-3 mo, every 3 mo until -36 mo
T: Auto BM-MNC Dose ? DPA, 1xC: ( – )
T: D, E, PST, BGM-MAC: D, E, PST, IIT, BGM-MA
HbA1c and C peptide in treatment were significantly better than either pre-therapy values or control.In Treatment:18/56 patients insulin was discontinued;19/56 insulin reduction > 50%, 10/56 insulin reduction 15-50%, 9/56 –non responderIn control: 40/62 patients – insulin requirement increased > 50%, 22/62 patients – increased 15-45%.
A license is required to provide regenerative medicine In order to provide regenerative medicine, based on the Act on Ensuring the Safety of Regenerative Medicine, a specific authorized regenerative medicine committee has It must be reviewed by the Ministry of Health, Labor and Welfare and accepted by the Ministry of Health, Labor and Welfare. Artisan Clinic Hibiya is a medical institution that has been accepted by the Ministry of Health, Labor and Welfare for a provision plan for knee joint stem cell administration.
