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Horm Metab Res 2023; 55(08): 536-545
DOI: 10.1055/a-2094-1039
Original Article: Endocrine Care

Adipose Tissue-Derived Stromal/Stem Cells Transplantation with Cholecalciferol Supplementation in Recent-Onset Type 1 Diabetes Patients: Twelve Months Follow-Up

Joana R. Dantas
1   Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
Debora Batista Araujo
1   Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
Karina Ribeiro Silva
2   Laboratory of Tissue Bioengineering, Instituto Nacional de Metrologia Qualidade e Tecnologia Campus de Xerem, Duque de Caxias, Brazil
3   Histology and Embryology Departament, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
,
Debora Lopes Souto
1   Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
Maria de Fatima Carvalho Pereira
1   Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
Luiz Ronir Raggio
4   Institute of Public Health Studies, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Cesar Claudio-da Silva
5   Plastic Surgery, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Carlos Eduardo Couri
6   Internal Medicine, Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto, Ribeirao Preto, Brazil
,
Angelo Maiolino
7   Hematology Department, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Carmen Lucia Kuniyoshi Rebellato
8   Core Cell Technology, Pontifical Catholic University of Parana, Curitiba, Brazil
,
Debora Regina Daga
8   Core Cell Technology, Pontifical Catholic University of Parana, Curitiba, Brazil
,
Alexandra Cristina Senegaglia
8   Core Cell Technology, Pontifical Catholic University of Parana, Curitiba, Brazil
,
Paulo Roberto Slud Brofman
8   Core Cell Technology, Pontifical Catholic University of Parana, Curitiba, Brazil
,
Leandra S. Baptista
2   Laboratory of Tissue Bioengineering, Instituto Nacional de Metrologia Qualidade e Tecnologia Campus de Xerem, Duque de Caxias, Brazil
9   Center for Biological Research (Numpex-Bio), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
,
Jose Egidio Paulo de Oliveira
1   Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
Lenita Zajdenverg
1   Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
,
Melanie Rodacki
1   Nutrology and Diabetes Department, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
› Author Affiliations Fundings Coordenação de Aperfeiçoamento de Pessoal de Nível Superior — http://dx.doi.org/10.13039/501100002322; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro — http://dx.doi.org/10.13039/501100004586;
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Abstract

To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation with cholecalciferol (VITD) in patients with recent-onset type 1 diabetes (T1D). Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1xKgx106 cells) and VITD 2000UI/day for 12 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve (CPAUC), insulin dose, HbA1c and frequency of FoxP3+ in CD4+ or CD8+ T-cells(flow cytometry) were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12). Eleven patients completed follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24±0.18vs0.53±0.23UI/kg,p=0.04), T6(0.24±0.15vs0.66±0.33 UI/kg,p=0.04) and T12(0.39±0.15vs0.74±0.29 UI/Kg,p=0.04).HbA1c was lower at T6 (50.57±8.56vs72.25±10.34 mmol/mol,p=0.01), without differences at T12 (57.14±11.98 in group 1 vs. 73.5±14.57 mmol/min in group 2, p=0.16). CPAUC was not significantly different between groups at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23). IDAA1c was significantly lower in group 1 than group 2 at T3,T6 and T12 (p=0.006, 0.006 and 0.042, respectively). IDDA1c was inversely correlated to FoxP3 expression in CD4 and CD8+ T cells at T6 (p<0.001 and p=0.01, respectively). In group 1, one patient had recurrence of a benign teratoma that was surgically removed, not associated to the intervention. ASCs with VITD without immunosuppression were safe and associated lower insulin requirements, better glycemic control, and transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained.

Key words

diabetes mellitus type 1 - stem cells - vitamin D - insulin secretion

Supplementary Material



Publication History

Received: 02 January 2023

Accepted after revision: 15 May 2023

Accepted Manuscript online:
16 May 2023

Article published online:
29 June 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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