ABRM Regenerative Medicine Board

Certification Review Course

Module V-F Endocrine Regenerative Medicine

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 Common Endocrine Conditions

• Diabetes Mellitus
• Type I
• Type II
• Osteoporosis
• Addison’s Disease
• Graves Disease
• Hashimoto Thyroiditis

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Diabetes Mellitus

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 Diabetes Mellitus

• Diabetes Mellitus
• Type I
• Autoimmune
• Pancreatic beta cell destruction
• Typically 70-80%
• Type II
• Insulin resistance
• Reduced Insulin secretion
• Strong inflammatory component

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 Pancreatic Beta Cells

• Islet/Beta Cells
• Predominant cell type in pancreatic islets
• Glucose homeostasis
• Synthesize, store and release insulin
• Release 30-70U of insulin per day

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Islets of Langerhans

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 Stem Cells and Diabetes Mellitus

Clinical efficacy of stem-cell therapy on diabetes mellitus: A systematic review and

meta-analysis
• Purpose
• This systematic literature review aims to compare the efficacy and safety of traditional and stem
cell (SC) therapies for type 1 (T1DM) and type 2 (T2DM) diabetes mellitus patients
• Methods
• 38 original articles were selected, which included 647 control cases and 654 treatments
• Outcome measures
• Insulin requirements
• Glycosylated Hg
• Fasting blood glucose
• C-Peptide

Pires IGS, Silva E Souza JA, de Melo Bisneto AV, Passos XS, Carneiro CC. Clinical efficacy of stem-cell therapy on
diabetes mellitus: A systematic review and meta-analysis. Transpl Immunol. 2022 Dec;75:101740.

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 Stem Cells and Diabetes Mellitus

Clinical efficacy of stem-cell therapy on diabetes mellitus: A systematic review and

meta-analysis
• Results
• All SC treatments significantly reduced the need for insulin following 6 and 12 months of
treatment
• Fasting blood glucose and glycosylated hemoglobin levels were significantly reduced in all follow-
ups with SC
• SC treatment caused a significant increase in C-peptide levels
• Bone marrow hematopoietic stem cell therapy produced better results than the conventional drug
treatment for diabetes mellitus
• Conclusions
• The results with SC were significantly better, regardless of the follow-up period
• Studies have proven cell therapy to be beneficial, safe, and effective

Pires IGS, Silva E Souza JA, de Melo Bisneto AV, Passos XS, Carneiro CC. Clinical efficacy of stem-cell therapy on
diabetes mellitus: A systematic review and meta-analysis. Transpl Immunol. 2022 Dec;75:101740.
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 Stem Cells and Diabetes Mellitus

Efficacy of mesenchymal stem cell transplantation therapy for type 1 and type 2
diabetes mellitus: a meta-analysis
• Purpose
• This meta-analysis was conducted to evaluate the efficacy and safety of transplantation of
mesenchymal stem cells in the treatment of type 1 and type 2 diabetes mellitus (T1DM and T2DM)
• Methods
• We included 10 studies in our meta-analysis (4 studies on T1DM and 6 on T2DM, with 239
participants)
• Outcome measures
• Insulin requirements
• Glycosylated Hg
• Fasting blood glucose
• C-Peptide

Li Y, Wang F, Liang H, Tang D, Huang M, Zhao J, Yang X, Liu Y, Shu L, Wang J, He Z, Liu Y. Efficacy of mesenchymal stem cell
transplantation therapy for type 1 and type 2 diabetes mellitus: a meta-analysis. Stem Cell Res Ther. 2021 May 6;12(1):273

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 Stem Cells and Diabetes Mellitus

Efficacy of mesenchymal stem cell transplantation therapy for type 1 and type 2
diabetes mellitus: a meta-analysis
• Results
• According to the pooled estimates, the glycated hemoglobin (HbA1c) level of the MSC-treated
group was significantly lower than it was at baseline (P = 0.001)
• The fasting C-peptide level of the MSC-treated group with T1DM was higher than that of the
control group (P = 0.001)
• The insulin requirement was significantly lower than it was at baseline (P < 0.00001)
• Conclusions
• Transplantation of mesenchymal stem cells has beneficial effects on diabetes mellitus, especially
T1DM, and no obvious adverse reactions

Li Y, Wang F, Liang H, Tang D, Huang M, Zhao J, Yang X, Liu Y, Shu L, Wang J, He Z, Liu Y. Efficacy of mesenchymal stem cell
transplantation therapy for type 1 and type 2 diabetes mellitus: a meta-analysis. Stem Cell Res Ther. 2021 May 6;12(1):273

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 Stem Cells and Type I Diabetes Mellitus

Efficacy and safety of stem cells transplantation in patients with type 1 diabetes
mellitus-a systematic review and meta-analysis
• Purpose
• Systematic review and meta-analysis to evaluate the efficacy and safety of stem cells
transplantation (SCT) in patients with T1DM
• Methods
• 29 studies (487 patients with T1DM) were included in the meta-analysis
• Outcome measures
• Insulin requirements
• Glycosylated Hg
• C-Peptide

Wu Q, Zheng S, Qin Y, Zheng X, Chen H, Yang T, Zhang M. Efficacy and safety of stem cells transplantation in patients with type 1
diabetes mellitus-a systematic review and meta-analysis. Endocr J. 2020 Aug 28;67(8):827-840

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 Stem Cells and Type I Diabetes Mellitus

Efficacy and safety of stem cells transplantation in patients with type 1 diabetes
mellitus-a systematic review and meta-analysis
• Results
• SCT had significant effect to decrease HbA1c (p < 0.00001) and to improve C-peptide levels (p =
0.04) at 1 year follow-up
• Significant improvement of metabolic outcomes was observed in the subgroups of mesenchymal
stem cells (MSCs) combined with hematopoietic stem cells (HSCs) and HSCs
• Older age showed significant association with the efficacy in HSCs subgroup
• The mean length of insulin independence was 15.6 months (95% CI: 12.3-18.9)
• Conclusions
• SCT is an efficacious and safe method for treating patients with T1DM especially in the subgroups
of MSCs + HSCs and HSCs

Wu Q, Zheng S, Qin Y, Zheng X, Chen H, Yang T, Zhang M. Efficacy and safety of stem cells transplantation in patients with type 1
diabetes mellitus-a systematic review and meta-analysis. Endocr J. 2020 Aug 28;67(8):827-840

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 Wharton’s Jelly MSCs and T2DM

Long term effect and safety of Wharton's jelly-derived mesenchymal stem cells on
type 2 diabetes
• Purpose
• The present study evaluated the long-term efficacy and safety of infusion of Wharton's jelly-
derived mesenchymal stem cells (WJ-MSC) on T2DM
• Methods
• A total of 61 patients with T2DM were randomly divided into two groups on the basis of basal
therapy
• patients in group I were administered WJ-MSC intravenous infusion twice, with a four-week interval
• patients in group II were treated with normal saline as control.
• Outcome measures
• Blood glucose, glycosylated hemoglobin, C-peptide, homeostasis model assessment of pancreatic islet β-
cell function and incidence of diabetic complications

Hu J, Wang Y, Gong H, Yu C, Guo C, Wang F, Yan S, Xu H. Long term effect and safety of Wharton's jelly-derived
mesenchymal stem cells on type 2 diabetes. Exp Ther Med. 2016 Sep;12(3):1857-1866

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 Wharton’s Jelly MSCs and T2DM

Long term effect and safety of Wharton's jelly-derived mesenchymal stem cells on
type 2 diabetes
• Results
• Blood glucose, glycosylated hemoglobin, C-peptide, homeostasis model assessment of pancreatic
islet β-cell function and incidence of diabetic complications in group I were significantly improved,
as compared with group II during the 36-month follow-up
• Conclusions
• The results of the present study demonstrated that infusion of WJ-MSC improved the function of
islet β-cells and reduced the incidence of diabetic complications
• The infusion of WJ-MSC may be an effective option for the treatment of patients with type 2
diabetes

Hu J, Wang Y, Gong H, Yu C, Guo C, Wang F, Yan S, Xu H. Long term effect and safety of Wharton's jelly-derived
mesenchymal stem cells on type 2 diabetes. Exp Ther Med. 2016 Sep;12(3):1857-1866

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 Umbilical Cord Derived Stem Cells and DM

Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a

meta-analysis study
• Purpose
• This meta-analysis study aims to provide a focused assessment for therapeutic efficacy of umbilical
cord (UC)-derived SC-transplantation, namely Wharton's jelly mesenchymal stem cells (WJ-MSCs)
and umbilical cord blood (UCB) for DM
• Methods
• 11 clinical studies were included; WJ-MSCs (6 studies; 172 patients including 71 controls) and UCB
(5 studies; 74 patients including 15 controls)
• Outcome measures
• Insulin requirements
• Glycosylated Hg
• C-Peptide

Kassem DH, Kamal MM. Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a meta-
analysis study. Stem Cell Res Ther. 2020 Nov 16;11(1):484.
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 Umbilical Cord Derived Stem Cells and DM

Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a

meta-analysis study
• Results
• WJ-MSCs significantly improved HbA1c% (pooled-estimate - 1.085; 95%CI (p < 0.001) and C-
peptide levels (p < 0.001), as well as the daily insulin-requirement (p = 0.002)
• UCB was found to be uniformly ineffective; HbA1c% (p = 0.622), significantly deteriorated C-
peptide levels (p < 0.001) and daily insulin-requirement (p = 0.007)
• Observations remained consistent in the sub-group meta-analysis for T1DM and T2DM and also
when comparing patients who received WJ-MSCs or UCB to controls
• Conclusions
• The results of the meta-analysis provide a clear evidence for the superior efficacy of WJ-MSCs over
UCB in DM

Kassem DH, Kamal MM. Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a meta-
analysis study. Stem Cell Res Ther. 2020 Nov 16;11(1):484.
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 Diabetes Mellitus Summary

• Level I Evidence
• The results with SC were significantly better, regardless of the follow-up period
• Studies have proven cell therapy to be beneficial, safe, and effective
• The results demonstrated that infusion of WJ-MSC improved the function of islet β-cells
and reduced the incidence of diabetic complications
• The infusion of WJ-MSC may be an effective option for the treatment of patients with
type 2 diabetes
Osteoporosis
Osteoporosis

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 Stem Cells and Osteoporosis

Safety and efficacy of Wharton's jelly-derived mesenchymal stem cells with

teriparatide for osteoporotic vertebral fractures: A phase I/IIa study
• Purpose
• Conducted a randomized, open-label, phase I/IIa study to determine the feasibility, safety, and effectiveness of
Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) and teriparatide (parathyroid hormone 1-34) in
OVCFs
• Methods
• 20 subjects with recent OVCFs were randomized to teriparatide (20 μg/day, daily subcutaneous injection for 6
months) treatment alone or combined treatment of WJ-MSCs (intramedullary [4 × 107 cells] injection and
intravenous [2 × 108 cells] injection after 1 week) and teriparatide (20 μg/day, daily subcutaneous injection for
6 months).
• 14 subjects (teriparatide alone, n = 7; combined treatment, n = 7) completed follow-up assessment (visual
analog scale [VAS], Oswestry Disability Index [ODI], Short Form-36 [SF-36], bone mineral density [BMD], bone
turnover measured by osteocalcin and C-terminal telopeptide of type 1 collagen, dual-energy x-ray
absorptiometry [DXA], computed tomography [CT])

Shim J, Han I. Safety and efficacy of Wharton's jelly-derived mesenchymal stem cells with teriparatide for
osteoporotic vertebral fractures: A phase I/IIa study. Stem Cells Transl Med. 2021 Apr;10(4):554-567

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 Stem Cells and Osteoporosis

Safety and efficacy of Wharton's jelly-derived mesenchymal stem cells with

teriparatide for osteoporotic vertebral fractures: A phase I/IIa study
• Results
• Combined treatment with WJ-MSCs and teriparatide is feasible and tolerable for the patients with
OVCFs
• The mean VAS, ODI, and SF-36 scores significantly improved in the combined treatment group
• Baseline spine CT images and follow-up CT images at 6 and 12 months showed better
microarchitecture in the combined treatment group
• Conclusions
• Results indicate that combined treatment of WJ-MSCs and teriparatide is feasible and tolerable
and has a clinical benefit for fracture healing by promoting bone architecture

Shim J, Han I. Safety and efficacy of Wharton's jelly-derived mesenchymal stem cells with teriparatide for
osteoporotic vertebral fractures: A phase I/IIa study. Stem Cells Transl Med. 2021 Apr;10(4):554-567

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ABRM Regenerative Medicine Board
Certification Review Course

Module V-F Endocrine Regenerative Medicine

Copyright AARMEI 2023