Clinical benefits of autologous haematopoietic stem cell transplantation in type 1 diabetes patients

Gu, Bin; Miao, Huijie; Zhang, Jihao; Hu, Jiong; Zhou, Wenlong; Gu, Wei; Wang, Wandong; Ning, Guang

doi:10.1016/j.diabet.2017.12.006

Cited by 23 publications

(23 citation statements)

References 26 publications

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“…To eliminate the honeymoon period, we analyzed RR from the 4 RCT studies, the result suggested the SCT showed significant effect to improve insulin independence rate compared to control group. Among the 4 RCT studies, only one patient achieved 7months insulin independence in the insulin group [42]. Thus, we preliminary draw the conclusion that SCT might prolong the insulin independence in T1DM.…”

Section: Discussionmentioning

confidence: 73%

“…The common adverse events contained alopecia, fever, vomiting, nausea, gastric tract symptoms, leucopenia, rash and diarrhea. Gu et al reported that most of the early adverse events were caused by the mobilization and conditioning drugs used during HSCs transplantation, whereas later adverse events were unremarkable compared with patients using insulin therapy [42]. D'Addio et al found that, most of the adverse events due to the administration of a high-dose immunosuppressive regimen.…”

Section: Discussionmentioning

confidence: 99%

“…Yu WL et al [22] also observed 3 patients achieving insulin independence after SCT, but did not reported the mean period. Among the 11 studies, only 4 were randomized controlled trials (RCT) [22,28,33,42], the others were self-controlled trails. When analyzing the insulin independence rate in the RCT studies, the SCT showed the significant effects to improve the insulin independence rate compared to control group which treated with insulin (risk ratio (RR), 9.67; 95% CI, 2.62 to 35.62; p = 0.001; I 2 = 0%).…”

Section: Insulin Independent Ratementioning

confidence: 99%

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Efficacy and safety of stem cells transplantation in patients with type 1 diabetes mellitus—a systematic review and meta-analysis

Zheng

Yao

et al. 2020

Endocr J

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Stem cells (SCs) therapy is a new promising therapeutic modality for type 1 diabetes (T1DM). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of stem cells transplantation (SCT) in patients with T1DM. We searched five literature databases (MEDLINE, EMBASE, Web of Science, WanFang and CENTRAL) up to 31 October 2019. 29 studies (487 patients with T1DM) were included in our meta-analysis. There was no substantial publication bias. Meta-analysis showed the SCT had significant effect to decrease HbA1c (SMD, 1.40; 95% CI, 0.93 to 1.86; p < 0.00001; I 2 = 89%) and to improve C-peptide levels (SMD,-0.62; 95% CI,-1.22 to-0.02; p = 0.04; I 2 = 92%) at 1 year follow-up. Subgroup analyses showed the heterogeneity level of the results was high. Significant improvement of metabolic outcomes was observed in the subgroups of mesenchymal stem cells (MSCs) combined with hematopoietic stem cells (HSCs) and HSCs. The older age showed significant association with the efficacy in HSCs subgroup. The higher GADA positive rate before treatment also significantly associated with the decrease of daily insulin requirement. The transient insulin independence rate at last follow-up was 9.6 per 100 person-years (95% CI: 5.8-13.5%). The mean length of insulin independence was 15.6 months (95% CI: 12.3-18.9). The mortality of SCT was 3.4% (95% CI: 2.1-5.5%). Therefore, SCT is an efficacious and safe method for treating patients with T1DM especially in the subgroups of MSCs + HSCs and HSCs. Well designed, double blind and randomized controlled trails with large sample size and long-term follow-up are needed for further evaluation.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Insulin Independent Ratementioning

confidence: 99%

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Efficacy and safety of stem cells transplantation in patients with type 1 diabetes mellitus—a systematic review and meta-analysis

Zheng

Yao

et al. 2020

Endocr J

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“…Although the etiology of this disease is still under study, most scientists agree that T2DM is related to the resistance of insulin in muscle cells; briefly, insulin cannot trigger the glucose uptake process into cells 7,16 . For the past decade of stem cell therapy, most studies have used stem cell therapy in type 1 diabetes mellitus to regenerate beta cells in the pancreas [17][18][19] . In recent years, some studies have evaluated the use of stem cells to treat T2DM 14 .…”

Section: Discussionmentioning

confidence: 99%

A type 2 diabetes mellitus patient was successfully treated by autologous bone marrow-derived stem cell transplantation: A case report

Doan

Tien

et al. 2019

Biomed. Res. Ther.

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Introduction: Type 2 diabetes mellitus (T2DM) iscurrently one of the most common diseases as a result of obesity and aging. Currently, T2DMis treated by various methods, such as insulin injection and glucose regulation agents. In this report, we report the case of a T2DM patient who was successfully treated by autologous bone marrow-derived stem cell transplantation. Methods: The patient was diagnosed with T2DM by standard methods for more than ten years. The patient agreed to be treated by the new approach – autologous bone marrow-derived stem cell transplantation. The bone marrow was collected from the patient twice at 100 mL volume each time. The stem cellenriched mononuclear cells (MNCs) in the bone marrow were isolated by gradient centrifugation. MNCs were intravenously transfused into the patient twice within the 1-month interval. The lasting glucose and 2h-after meal glucose, as well as hemoglobin A1c (Hab1c), were recorded before transplantation, and 1-, 3-, and 6-months post-transplantation. Results: The results showed that there were no adverse effect recorded during the monitoring period, and that the T2DM symptoms significantly improved. After the first round of transplantation, the glucose level reduced considerably and continued to decrease out to 3 months. Meanwhile, after 2 months of transplantation, the Hab1C level decreased and achieved the average level at the 3rd month of treatment. After 6 months, the patient was free from insulin injection and maintained glucose and Hab1c level. To date, after 9 months of treatment; the patients has continued to be free from insulin injection and without any adverse effects. Conclusion: The primary results have suggested that autologous bone marrow-derived stem cell transplantation may be a new direction for T2DM treatment.

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“…The prospect of successful cell therapy has recently gained greater footing in the medical landscape in the past 2 years with the arrival of many cell-based products. Recently, many AHSCT-related clinical trials have demonstrated a beneficial effect in the treatment of several autoimmune diseases, and AHSCT is now considered one of the few therapies capable of reversing T1D in humans ( 6 , 14 , 25 – 27 ). In our study, we observed preservation of β cell function following AHSCT, as most patients included in our study population exhibited a sustained and adequate postprandial C-peptide response.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes

et al. 2018

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Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only “experimental therapy” that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes.

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Clinical benefits of autologous haematopoietic stem cell transplantation in type 1 diabetes patients

Cited by 23 publications

References 26 publications

Efficacy and safety of stem cells transplantation in patients with type 1 diabetes mellitus—a systematic review and meta-analysis

Efficacy and safety of stem cells transplantation in patients with type 1 diabetes mellitus—a systematic review and meta-analysis

A type 2 diabetes mellitus patient was successfully treated by autologous bone marrow-derived stem cell transplantation: A case report

Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes

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