Regenerative Medicine Program, Doctors Hospital Health System, Nassau, Bahamas.
National Stem Cells Ethic Committee (NSCEC), Ministry of Health, Nassau, Bahamas.
Med Sci Monit. 2023 Jan 20;29:e938979. doi: 10.12659/MSM.938979.
BACKGROUND Bone marrow stem cells have been shown to be a promising therapeutic strategy for autoimmune diseases. This study aimed to assess the safety and efficacy of autologous hematopoietic stem cell (ABMSC) transplantation without immunoablation used to suppress the autoimmune reaction in 6 children with newly diagnosed autoimmune diabetes mellitus. We monitored the levels of islet cell antibodies (ICA), antibodies against islet antigen-related tyrosine phosphatase 2 (IA2), glutamic acid-decarboxylase (GAD) antibodies, and anti-insulin antibodies (AIA). MATERIAL AND METHODS Between 2018 and 2022, 6 children (age 6-10 years, average 8 years) recently diagnosed with type 1 diabetes mellitus with the presence of ICA, IA2, GAD, AIA and ketoacidosis, were treated with an ABMSC stimulated with Filgrastim, granulocyte colony-stimulating factor (G-CSF), 10 ug/kg/day for 4 days. Bone marrow was harvested on day 5, collected by puncture and identified as mononuclear cells >180×10⁶/kg, CD34+ >0.22%, and transplanted by intravenous (i.v.) infusion. Patients were monitored with ICA, IA2, GAD, AIA, C-peptide, blood glucose, and glycosylated hemoglobin A1c (HbA1C) 6 months after the procedure. RESULTS At 6-month follow-up, we observed a negative value of the ICA, which was previously positive (P<0.001). The IA2 (p=0.037) and GAD (P=0.377) antibodies decreased slowly but were significantly lower. AIA remained high. A decrease in blood glucose and HbA1C levels was observed (P<0.001). No complications occurred during follow-up. CONCLUSIONS Autologous hematopoietic stem cell transplantation without immunoablation was safe and effective in significantly decreasing the production and effect of autoantibodies against ICA, GAD, and IA2, as well as decreasing blood sugar levels and HbA1c.
骨髓干细胞已被证明是治疗自身免疫性疾病的一种有前途的治疗策略。本研究旨在评估在 6 名新诊断为自身免疫性糖尿病的儿童中,使用未经免疫消融的自体造血干细胞(ABMSC)移植来抑制自身免疫反应的安全性和有效性。我们监测了胰岛细胞抗体(ICA)、胰岛抗原相关酪氨酸磷酸酶 2(IA2)抗体、谷氨酸脱羧酶(GAD)抗体和抗胰岛素抗体(AIA)的水平。
在 2018 年至 2022 年期间,我们治疗了 6 名年龄在 6-10 岁(平均 8 岁)、新诊断为伴有 ICA、IA2、GAD、AIA 和酮症酸中毒的 1 型糖尿病儿童,使用 Filgrastim、粒细胞集落刺激因子(G-CSF)刺激 ABMSC,每天 10ug/kg,连续 4 天。第 5 天采集骨髓,通过穿刺采集并鉴定为单核细胞>180×10⁶/kg、CD34+>0.22%,通过静脉(i.v.)输注进行移植。患者在手术后 6 个月进行 ICA、IA2、GAD、AIA、C-肽、血糖和糖化血红蛋白 A1c(HbA1C)监测。
在 6 个月的随访中,我们观察到之前阳性的 ICA 值变为阴性(P<0.001)。IA2(p=0.037)和 GAD(p=0.377)抗体缓慢下降,但显著降低。AIA 仍保持高水平。观察到血糖和 HbA1C 水平降低(P<0.001)。随访期间未发生并发症。
未经免疫消融的自体造血干细胞移植在显著降低 ICA、GAD 和 IA2 自身抗体的产生和作用以及降低血糖和 HbA1c 水平方面是安全有效的。