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Review
. 2021 Jul 9:12:694118.
doi: 10.3389/fimmu.2021.694118. eCollection 2021.

Hematopoietic Stem Cells in Type 1 Diabetes

Ida Pastore  1 , Emma Assi  2 , Moufida Ben Nasr  2   3 , Andrea Mario Bolla  1 , Anna Maestroni  2 , Vera Usuelli  2 , Cristian Loretelli  2 , Andy Joe Seelam  2 , Ahmed Abdelsalam  2 , Gian Vincenzo Zuccotti  1   4 , Francesca D'Addio  1   2 , Paolo Fiorina  1   2   3
Affiliations
Review

Hematopoietic Stem Cells in Type 1 Diabetes

Ida Pastore et al. Front Immunol. .

Abstract

Despite the increasing knowledge of pathophysiological mechanisms underlying the onset of type 1 diabetes (T1D), the quest for therapeutic options capable of delaying/reverting the diseases is still ongoing. Among all strategies currently tested in T1D, the use of hematopoietic stem cell (HSC)-based approaches and of teplizumab, showed the most encouraging results. Few clinical trials have already demonstrated the beneficial effects of HSCs in T1D, while the durability of the effect is yet to be established. Investigators are also trying to understand whether the use of selected and better-characterized HSCs subsets may provide more benefits with less risks. Interestingly, ex vivo manipulated HSCs showed promising results in murine models and the recent introduction of the humanized mouse models accelerated the translational potentials of such studies and their final road to clinic. Indeed, immunomodulatory as well as trafficking abilities can be enhanced in genetically modulated HSCs and genetically engineered HSCs may be viewed as a novel "biologic" therapy, to be further tested and explored in T1D and in other autoimmune/immune-related disorders.

Keywords: NOD mouse model; autoimmune response; genetic modulation; hematopoietic stem cells; type 1 diabetes.

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Conflict of interest statement

PF and MB hold a patent of modulated HSCs and founded Altheia Science. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Complete/partial remission of type 1 diabetes obtained with AHSCT in the long-term. Proposed genetic engineered HSC-based approach to target type 1 diabetes. (A) Proportion of patients with T1D undergoing AHSCT who achieved complete remission (insulin independence) and partial remission (low dose exogenous insulin requirement) at the latest timepoint analyzed within each clinical study registered in ClinicalTrials.gov available as publication. (B) Use of genetically engineered HSCs to target T1D: proposed approach. T1D, type 1 diabetes; AHSCT, autologous hematopoietic stem cell transplantation.
See this image and copyright information in PMC

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