Stem Cell Transplantation in the Treatment of Type 1 Diabetes Mellitus: From Insulin Replacement to Beta-Cell Replacement

Wan, Xinxing; Zhang, Dan-Yi; Zheng, Sheng-Yuan; Hu, Xi-Min; Zhang, Qi; Yang, Ronghua; Xiong, Kun

doi:10.3389/fendo.2022.859638

Cited by 39 publications

(13 citation statements)

References 121 publications

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“…Stem cell intervention before transplantation might help maintain cells and restructure the immune response since immunosuppression altered the effect of stem cell transplantation. [86] The cotransplantation of mesenchymal stem cells and islet cells, as well as genetically modified pluripotent stem cells, have recently made significant strides in improving the efficacy of stem cell transplantation processes. These developments have also provided powerful tools for the study of the mechanisms underlying diabetes and disease modeling.…”

Section: Cell Therapy In Diabetesmentioning

confidence: 99%

Current Advances in Immunomodulatory Biomaterials for Cell Therapy and Tissue Engineering

Kim,

Pradhan,

Hernandez

et al. 2023

Advanced Therapeutics

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Biomaterials have gained immense attention for various diseases due to their unique advantages over chemical drugs regarding cost, ease of production, toxicity, and therapeutic efficacy. However, these materials need an inert delivery system that locally delivers cells and minimally elicits foreign body response (FBR). In this aspect, various immunomodulatory biomaterials, including silk, collagen, fibrin, hyaluronic acid, and alginate-based biomaterials, have great potential due to large natural sources, ease of extraction, low cost, chemical inertness, facile surface functionalization, long-term polymeric stability, high biocompatibility, and fine tunability of biomaterials sizes and shapes. In this review article, the recent advancements in the biomedical applications of immunomodulatory biomaterials in different diseases, including diabetes, cancer, cardiovascular disease, bone regeneration, etc, are highlighted. Moreover, the FBR on immunomodulatory biomaterials is discussed and the current and future strategies for the potential mitigation of considerable immune responses toward immunomodulatory biomaterials and devices are highlighted.Recently, with development in cell therapies, stem cell biology, biomaterials, and advanced fabrication techniques, there has been a surge in the use of biomaterials in many healthcare

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Section: Cell Therapy In Diabetesmentioning

confidence: 99%

Current Advances in Immunomodulatory Biomaterials for Cell Therapy and Tissue Engineering

Kim,

Pradhan,

Hernandez

et al. 2023

Advanced Therapeutics

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show abstract

“…The former consists of a pool of different kinds of cells, typically obtained by bone marrow aspiration from the iliac crest, in which CD34 + cells represent a fraction of about 0.5–6% and are most likely responsible for the therapeutic effect [ 33 , 34 ]. On the other hand, MSCs are multipotent cells that can differentiate in several cell types, such as osteoblasts, chondroblasts, myocytes, adipocytes and β-cell-like cells [ 17 , 35 , 36 , 37 ]; can be collected from various tissues, including bone marrow, fat and umbilical cord blood; and possess immunomodulatory properties and the potential to protect pancreatic islets and promote their regeneration [ 38 , 39 , 40 ].…”

Section: Hematopoietic Stem/progenitor Cells For Cell Therapymentioning

confidence: 99%

Human Hematopoietic Stem/Progenitor Cells in Type One Diabetes Mellitus Treatment: Is There an Ideal Candidate?

Carulli

Pompilio

Vinci

2023

Cells

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Type 1 diabetes mellitus (T1DM) is a highly prevalent autoimmune disease causing the destruction of pancreatic islet β-cells. The resulting insulin production deficiency leads to a lifelong need for insulin re-placement therapy, systemic complications, and reduced life quality and expectancy. Cell therapy has been extensively attempted to restore insulin independence (IID), and autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) has appeared to give the most promising results, but with a highly variable quote of patients achieving IID across the studies. We performed a comprehensive review of the trials involving stem cells, and in particular AHST, for the treatment of T1DM. We then pooled the patients enrolled in the different trials and looked for the patient characteristics that could be associated with the achievement of IID. We found a significantly higher probability of achieving IID in older patients (OR 1.17, 95%CI 1.06–1.33, p = 0.002) and a significantly lower probability in patients with a history of ketoacidosis (OR 0.23, 95%CI 0.06–0.78, p = 0.023). This suggests that there could be a population of patients more likely to benefit from AHST, but further data would be required to depict the profile of the ideal candidate.

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“…Clinical good-manufacturing practice (cGMP)-grade stem cell products have been used in human clinical trials, showing that stem cell transplantation has beneficial effects on T1D, with no obvious adverse reactions. To better achieve remission of T1D by stem cell transplantation, innovative approaches such as mesenchymal stem cells (MSCs), human embryonic stem cells (hESCs), and bone marrow hematopoietic stem cells (BM-HSCs) to restore the immunotolerance and preserve the islet beta-cell function of T1D have been investigated [ 63 ], but the results are, up to now, discouraging.…”

Section: Stem Cell Graftingmentioning

confidence: 99%

Insulitis in Human Type 1 Diabetic Pancreas: From Stem Cell Grafting to Islet Organoids for a Successful Cell-Based Therapy

Noce

Nicoletti

Papaccio

et al. 2022

Cells

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Type 1 diabetes (T1D) is an autoimmune disease with immune cells’ islet infiltration (called “insulitis”), which leads to beta cell loss. Despite being the critical element of T1D occurrence and pathogenesis, insulitis is often present in a limited percentage of islets, also at diagnosis. Therefore, it is needed to define reproducible methods to detect insulitis and beta-cell decline, to allow accurate and early diagnosis and to monitor therapy. However, this goal is still far due to the morphological aspect of islet microvasculature, which is rather dense and rich, and is considerably rearranged during insulitis. More studies on microvasculature are required to understand if contrast-enhanced ultrasound sonography measurements of pancreatic blood-flow dynamics may provide a clinically deployable predictive marker to predict disease progression and therapeutic reversal in pre-symptomatic T1D patients. Therefore, it is needed to clarify the relation between insulitis and the dynamics of β cell loss and with coexisting mechanisms of dysfunction, according to clinical stage, as well as the micro vessels’ dynamics and microvasculature reorganization. Moreover, the ideal cell-based therapy of T1D should start from an early diagnosis allowing a sufficient isolation of specific Procr+ progenitors, followed by the generation and expansion of islet organoids, which could be transplanted coupled to an immune-regulatory therapy which will permit the maintenance of pancreatic islets and an effective and long-lasting insulitis reversal.

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Stem Cell Transplantation in the Treatment of Type 1 Diabetes Mellitus: From Insulin Replacement to Beta-Cell Replacement

Cited by 39 publications

References 121 publications

Current Advances in Immunomodulatory Biomaterials for Cell Therapy and Tissue Engineering

Current Advances in Immunomodulatory Biomaterials for Cell Therapy and Tissue Engineering

Human Hematopoietic Stem/Progenitor Cells in Type One Diabetes Mellitus Treatment: Is There an Ideal Candidate?

Insulitis in Human Type 1 Diabetic Pancreas: From Stem Cell Grafting to Islet Organoids for a Successful Cell-Based Therapy

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