The Feasibility and Applicability of Stem Cell Therapy for the Cure of Type 1 Diabetes

Inoue, Ryota; Nishiyama, Kuniyuki; Li, Jinghe; Miyashita, Daisuke; Ono, Masato; Terauchi, Yasuo; Shirakawa, Jun

doi:10.3390/cells10071589

Cited by 9 publications

(7 citation statements)

References 107 publications

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“…Further research on their effect within the context of MSCs transplantation in T1D models is necessary, considering that these drugs are suggested to have negative effects on β-cells proliferation [56,57]. If ISDs are not required following MSC transplantation, the associated medical care costs would be reduced while improving the patient quality of life [58]. It should also be noted that the development of IPC cell therapy requires the encapsulation of islet cells and nanotechnology that can safely deliver them and protect them against immune cells [59][60][61][62].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

Park

Yang²,

Cho³

2022

IJMS

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In patients with type 1 diabetes (T1D), compromised pancreatic β-cell functions are compensated through daily insulin injections or the transplantation of pancreatic tissue or islet cells. However, both approaches are associated with specific challenges. The transplantation of mesenchymal stem cells (MSCs) represents a potential alternative, as MSCs have tissue-forming capacity and can be isolated from various tissues. The human umbilical cord (hUC) is a good source of freely available MSCs, which can be collected through pain-free, non-invasive methods subject to minimal ethical concerns. We sought to develop a method for the in vitro generation of insulin-producing cells (IPCs) using MSCs. We examined the potential therapeutic uses and efficacy of IPCs generated from hUC-derived MSCs (hUC-IPCs) and human adipose tissue (hAD)-derived MSCs (hAD-IPCs) through in vitro experiments and streptozotocin (STZ)-induced C57BL/6 T1D mouse models. We discovered that compared to hAD-IPCs, hUC-IPCs exhibited a superior insulin secretion capacity. Therefore, hUC-IPCs were selected as candidates for T1D cell therapy in mice. Fasting glucose and intraperitoneal glucose tolerance test levels were lower in hUC-IPC-transplanted mice than in T1D control mice and hAD-IPC-transplanted mice. Our findings support the potential use of MSCs for the treatment of T1D.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

Park

Yang²,

Cho³

2022

IJMS

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“…The second disadvantage is that there is a potential for the transplanted cells to become cancerous. The c-Myc gene, one of the Yamanaka factors, is known to cause cancer in iPSCs ( 115 ), but oncogenesis can be prevented by using L-Myc instead of the c-Myc gene ( 116 ). The third limitation is the possibility that the insulin secretion of the transplanted cells may be insufficient.…”

Section: Stem Cells As the Next Alternative Source To Generate α And ...mentioning

confidence: 99%

“…In conclusion, SC beta cells for the treatment of T1D increase quality-adjusted life years ( 115 , 117 ) and prevent complications, although a reduction in manufacturing costs will be essential to achieve cost-effectiveness. By scaling up the manufacturing, as promised, facilitating the supply chain management, and reducing the manufacturing costs, iPSC-based β cell replacement therapies may become a tangible reality.…”

Section: Future Perspectivesmentioning

confidence: 99%

The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?

Naqvi

Naqvi²,

Singh³

et al. 2023

Front. Endocrinol.

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Replacement of β cells is only a curative approach for type 1 diabetes (T1D) patients to avoid the threat of iatrogenic hypoglycemia. In this pursuit, islet allotransplantation under Edmonton’s protocol emerged as a medical miracle to attain hypoglycemia-free insulin independence in T1D. Shortage of allo-islet donors and post-transplantation (post-tx) islet loss are still unmet hurdles for the widespread application of this therapeutic regimen. The long-term survival and effective insulin independence in preclinical studies have strongly suggested pig islets to cure overt hyperglycemia. Importantly, CRISPR-Cas9 technology is pursuing to develop “humanized” pig islets that could overcome the lifelong immunosuppression drug regimen. Lately, induced pluripotent stem cell (iPSC)-derived β cell approaches are also gaining momentum and may hold promise to yield a significant supply of insulin-producing cells. Theoretically, personalized β cells derived from a patient’s iPSCs is one exciting approach, but β cell-specific immunity in T1D recipients would still be a challenge. In this context, encapsulation studies on both pig islet as well as iPSC–β cells were found promising and rendered long-term survival in mice. Oxygen tension and blood vessel growth within the capsules are a few of the hurdles that need to be addressed. In conclusion, challenges associated with both procedures, xenotransplantation (of pig-derived islets) and stem cell transplantation, are required to be cautiously resolved before their clinical application.

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“…Human induced pluripotent stem cells (iPSCs) are proposed to overcome the limitations of a donor-based diabetes therapy, as they can be expanded extensively, and can be transferred to patients without immunosuppression [6,7]. However, the application of iPSCs requires complex and laborious differentiation protocols, and the resulting cells still lack in functionality [8].…”

Section: Introductionmentioning

confidence: 99%

“…The reconstitution of a 3D environment that mimics in vivo conditions, such as the formation of spheroids, improves the viability and proliferation of β‐cells, stabilizes their developmental fate, and most importantly enhances the glucose‐dependent insulin secretion [ 3 , 4 , 5 ]. Human induced pluripotent stem cells (iPSCs) are proposed to overcome the limitations of a donor‐based diabetes therapy, as they can be expanded extensively, and can be transferred to patients without immunosuppression [ 6 , 7 ]. However, the application of iPSCs requires complex and laborious differentiation protocols, and the resulting cells still lack in functionality [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

The cultivation conditions affect the aggregation and functionality of β‐cell lines alone and in coculture with mesenchymal stromal/stem cells

Petry

Salzig

2022

Engineering in Life Sciences

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The manufacturing of viable and functional β-cell spheroids is required for diabetes cell therapy and drug testing. Mesenchymal stromal/stem cells (MSCs) are known to improve β-cell viability and functionality. We therefore investigated the aggregation behavior of three different β-cell lines (rat insulinoma-1 cell line [INS-1], mouse insulinoma-6 cell line [MIN6], and a cell line formed by the electrofusion of primary human pancreatic islets and PANC-1 cells [1.1B4]), two MSC types, and mixtures of β-cells and MSCs under different conditions. We screened several static systems to produce uniform β-cell and MSC spheroids, finding cellrepellent plates the most suitable. The three different β-cell lines differed in their aggregation behavior, spheroid size, and growth in the same static environment.We found no major differences in spheroid formation between primary MSCs and an immortalized MSC line, although both differed with regard to the aggregation behavior of the β-cell lines. All spheroids showed a reduced viability due to mass transfer limitations under static conditions. We therefore investigated three dynamic systems (shaking multi-well plates, spinner flasks, and shaking flasks). In shaking flasks, there were no β-cell-line-dependent differences in aggregation behavior, resulting in uniform and highly viable spheroids. We found that the aggregation behavior of the β-cell lines changed in a static coculture with MSCs. The β-cell/MSC coculture conditions must be refined to avoid a rapid segregation into distinct populations under dynamic conditions.

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The Feasibility and Applicability of Stem Cell Therapy for the Cure of Type 1 Diabetes

Cited by 9 publications

References 107 publications

Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?

The cultivation conditions affect the aggregation and functionality of β‐cell lines alone and in coculture with mesenchymal stromal/stem cells

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