Effect of a single autologous cord blood infusion on beta-cell and immune function in children with new onset type 1 diabetes: a non-randomized, controlled trial

Giannopoulou, Eleni Z.; Puff, Ramona; Beyerlein, Andreas; Luettichau, Irene von; Boerschmann, Heike; Schatz, Desmond; Atkinson, Mark A.; Haller, Michael J.; Egger, Dietmar; Burdach, Stefan; Ziegler, Anette‐Gabriele

doi:10.1111/pedi.12072

Cited by 31 publications

(40 citation statements)

References 29 publications

(43 reference statements)

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“…Two smaller studies have evaluated the effect of non-expanded autologous umbilical cord blood transfusions into children with recent onset T1D [70,71]. Although well tolerated, neither demonstrated an impact on decline in beta cell function, likely due to an insufficient number of Tregs or loss of function with long-term storage of the cells.…”

Section: Source Of Tregsmentioning

confidence: 99%

Regulatory T cell therapy for type 1 diabetes: May the force be with you

Gitelman

Bluestone

2016

Journal of Autoimmunity

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a b s t r a c tType 1 diabetes mellitus (T1DM) results from autoimmune destruction of insulin producing beta cells. Regulatory T cells (Tregs) have been shown to be defective in this setting. Immuno-therapies targeting T cells, and resetting the balance between T effectors and Tregs, have had some initial success in preserving beta cell function. With a goal to use Tregs themselves as a novel therapeutic, we developed a technique to isolate and expand Tregs from patients with T1DM. These ex vivo expanded CD4 þ CD127 lo/À CD25 þ cells exhibit improved function and retain their T cell receptor diversity. These cells have subsequently been used in phase I clinical trials in patients with recent onset T1DM. The infusions were well tolerated, with no safety concerns. The studies are too small to assess efficacy definitively, although some individuals exhibit stable beta cell function over intervals as long as 2 years. These efforts set the stage for a larger phase II effort in new onset T1DM, and combination studies with other drugs, as well as efforts in other autoimmune diseases.

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Section: Source Of Tregsmentioning

confidence: 99%

Regulatory T cell therapy for type 1 diabetes: May the force be with you

Gitelman

Bluestone

2016

Journal of Autoimmunity

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“…Infusion of autologous UCB failed to preserve C‐peptide, reduce insulin dose, and decrease HbA1c level; only a transient rise in CD4 + CD25 + T reg cells was observed 6 months after UCB infusion . Researchers in Germany also performed the same trial and obtained almost the same results in T1DM patients with a disease duration <1 year . However, it was shown that there was a significant correlation between the change in the area under the curve for C‐peptide concentrations from baseline to 6‐months an the number of CD34 + UCB cells infused, suggesting that expansion of UCB CD34 + cells may provide potential cell therapy for T1DM …”

Section: Autologous Ucb Cell Transplantation For T1dmmentioning

confidence: 94%

“…16,17 Researchers in Germany also performed the same trial and obtained almost the same results in T1DM patients with a disease duration <1 year. 18 However, it was shown that there was a significant correlation between the change in the area under the curve for C-peptide concentrations from baseline to 6-months an the number of CD34 + UCB cells infused, suggesting that expansion of UCB CD34 + cells may provide potential cell therapy for T1DM. 18 Because animal and clinical studies suggest that vitamin D and docosahexaenoic acid (DHA) may play a role in preventing and treating T1DM, 40,41 researchers conducted another open-label randomized study in which patients received combination therapy of autologous UCB infusion and 1 year of daily supplementation with vitamin D and DHA.…”

Section: Autologous Ucb Cell Transplantation For T1dmmentioning

confidence: 99%

“…Cellular therapy is a method for replacing β ‐cells or targeting immune cells to restore immune balance. Based on the potential usefulness of umbilical cord blood (UCB) to re‐establish immune homeostasis, using UCB as a source of immunoregulatory cells has become increasingly popular in the treatment of autoimmune disorders . The present review focuses on current clinical and preclinical applications of UCB cell‐based therapy for T1DM.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic potential of umbilical cord blood cells for type 1 diabetes mellitus

et al. 2015

Journal of Diabetes

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Type 1 diabetes mellitus (T1DM) is a chronic disorder that results from autoimmune-mediated destruction of pancreatic islet β-cells. However, to date, no conventional intervention has successfully treated the disease. The optimal therapeutic method for T1DM should effectively control the autoimmunity, restore immune homeostasis, preserve residual β-cells, reverse β-cell destruction, and protect the regenerated insulin-producing cells against re-attack. Umbilical cord blood is rich in regulatory T (T(reg)) cells and multiple types of stem cells that exhibit immunomodulating potential and hold promise in their ability to restore peripheral tolerance towards pancreatic islet β-cells through remodeling of immune responses and suppression of autoreactive T cells. Recently, reinfusion of autologous umbilical cord blood or immune cells from cord blood has been proposed as a novel therapy for T1DM, with the advantages of no risk to the donors, minimal ethical concerns, a low incidence of graft-versus-host disease and easy accessibility. In this review, we revisit the role of autologous umbilical cord blood or immune cells from cord blood-based applications for the treatment of T1DM.

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“…CB is now stored in a growing number of banks, mainly as an immediately available and ethically acceptable source of hematopoietic stem cells [14]. Whole CB has also been assessed for therapy in some case studies of neurological disease [15], and in type 1 diabetes [16][17][18].…”

Section: Endocrine Carementioning

confidence: 99%

The Relative Merits of Cord Blood as a Cell Source for Autologous T Regulatory Cell Therapy in Type 1 Diabetes

et al. 2014

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Cord blood has been used as a cell source for therapeutic purposes in children with type 1 diabetes and other disorders. Here, we explore the benefits of cord blood as an autologous source of T regulatory cells for immune cell therapy in patients. CD4(+)CD25(+) T regulatory cells were isolated from cord blood and adult peripheral blood of healthy donors and compared during and after expansion in a 14-day protocol incorporating anti-CD3/anti-CD28 beads, and IL-2 with or without rapamycin. Cord blood T regulatory cells were largely naïve (89±7 vs. 31±10% in young adults, p<0.0001), and had higher expansion yields (median 5,968-fold) than adult T regulatory cells (median 516-fold, p=0.001) and adult naïve T regulatory cells (median 820-fold, p=0.003). Rapamycin reduced expansion yields, but was not necessary to obtain pure expanded cord blood T regulatory cells as judged by FOXP3 staining (94±3%), methylation status of FOXP3 (97%), and intracellular effector cytokine staining (< 6%). Expanded adult T regulatory cells were much less pure in the absence of rapamycin (72±19% FOXP3; 76% by methylation status, <13% INF-γ, <16% IL-4, <5% IL-17 positive), but purity was achieved by inclusion of rapamycin during expansion. Despite differences in purity, all preparations of expanded T regulatory from all sources were able to strongly suppress proliferation of T effector cells in vitro. Our findings suggest that cord blood is an excellent source of T regulatory cells for expansion and autologous cell therapy that may be considered as a strategy to prevent immune-mediated destruction of beta cells in type 1 diabetes.

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Effect of a single autologous cord blood infusion on beta-cell and immune function in children with new onset type 1 diabetes: a non-randomized, controlled trial

Abstract: An autologous cord blood infusion does not change the natural course of metabolic and immune parameters after disease onset. However, the content of CD34+ cells in the stored blood sample might offer potential for improvement of future cell therapies.

Cited by 31 publications

References 29 publications

Regulatory T cell therapy for type 1 diabetes: May the force be with you

Regulatory T cell therapy for type 1 diabetes: May the force be with you

Therapeutic potential of umbilical cord blood cells for type 1 diabetes mellitus

The Relative Merits of Cord Blood as a Cell Source for Autologous T Regulatory Cell Therapy in Type 1 Diabetes

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