Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells
Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells
复制标题
DOI：
10.1007/s10238-013-0266-1
复制
发表时间：
2015-02-01
影响因子：
4.6
通讯作者：
Chandra, T.
中科院分区：
文献类型：
--
作者：
Dave, S. D.;Vanikar, A. V.;Chandra, T.
胰岛素依赖型糖尿病（Insulin-dependent diabetes mellitus，IDDM）是一种代谢性疾病，通常由自身免疫介导的β细胞破坏引起，需要终生外源性胰岛素替代。骨髓间充质干细胞（MSC）是一种有前途的治疗方法。我们提出了我们的经验，治疗胰岛素依赖型糖尿病的联合输注自体脂肪组织来源的MSC分化的胰岛素分泌细胞（ISC）与造血干细胞（HSC）体外。这是一项机构审查委员会在获得10名患者的知情同意后批准的前瞻性非随机开放标签临床试验。从自体脂肪组织来源的MSC分化出ISC，并将骨髓来源的HSC通过小切口经门静脉、胸腺循环和皮下循环输注。监测患者的血糖水平、血清C肽水平、糖基化血红蛋白（Hb 1Ac）和谷氨酸脱羧酶（GAD）抗体。以滑动比例进行胰岛素施用，目标是维持FBS < 150 mg/dL和PPBS约200 mg/dL。输注了平均3.34 mL细胞接种物（5.25 x 10（4）个细胞/μ L）。未观察到不良反应。在平均31.71个月的随访期间，输注前平均血清C肽为0.22 ng/mL，持续升高0.92 ng/mL，外源性胰岛素需求从63.9国际单位（IU）/天降至38.6 IU/天。观察到平均Hb 1Ac从10.99%改善至6.72%。所有患者的平均GAD抗体均为阳性，平均值为331.10 IU/mL，降至平均值123 IU/mL。自体ISC与HSC的共输注代表了一种可行的治疗IDDM的新选择。
Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually resulting from autoimmune-mediated beta-cell destruction requiring lifetime exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising therapy. We present our experience of treating IDDM with co-infusion of in vitro autologous adipose tissue-derived MSC-differentiated insulin-secreting cells (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent from ten patients. ISC were differentiated from autologous adipose tissue-derived MSC and were infused with bone marrow-derived HSC in portal, thymic circulation by mini-laparotomy and in subcutaneous circulation. Patients were monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 x 10(4) cells/mu L were infused. No untoward effects were observed. Over a mean follow-up of 31.71 months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of 0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99 to 6.72 %. Mean GAD antibodies were positive in all patients with mean of 331.10 IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with HSC represents a viable novel therapeutic option for IDDM.