1 December 2009 in Stem Cells and Development
Progressive and inexorable β-cell dysfunction is the hallmark of type 2 diabetes mellitus (T2DM) and β-cell regeneration using stem cell therapy may prove to be an effective modality. A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (≥0.7 U/kg/day) at least for 1 year, and glutamic acid decarboxylase antibody negative were included. Patients on stable doses of medications for past 3 months were recruited. Primary end points were reduction in insulin requirement by ≥50% and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow–derived stem cell transplantation (SCT), while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline. Seven patients were responders and showed a reduction in insulin requirement by 75% as compared to baseline. Mean duration to achieve the primary objective was 48 days. Three patients were able to discontinue insulin completely, although it was short-lived in one. Mean HbA1c reduction was 1% and 3 of the 7 responders had HbA1c value <7%. A significant weight loss of 5.5 kg was noted in the responders, whereas, nonresponders gained 2.2 kg of weight. However, weight loss did not correlate with reduction in insulin requirement ( r = 0.68, P = 0.06). There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group ( P = 0.03) and responders ( P = 0.03). HOMA-B increased significantly in the whole group ( P = 0.02) and responders ( P = 0.04) whereas, HOMA-IR did not change significantly ( P = 0.74). Reduction in insulin doses correlated with stimulated C-peptide response at the baseline ( r = 0.83, P = 0.047) and mononuclear cell count of infused stem cells ( r = 0.57, P = 0.04). No serious adverse effects were noted. Our observations indicate that SCT is a safe and effective modality of treatment to improve β-cell function in patients with T2DM. However, further large-scale studies are needed to substantiate these observations.
1 September 2014 in Cell Transplantation
There is a growing interest in cell-based therapies in T2DM as β-cell failure is progressive and inexorable with the advancing duration of disease. This prospective, randomized, single-blinded placebo-controlled study evaluates the efficacy and safety of autologous bone marrow-derived stem cell transplantation (ABMSCT) in T2DM. Twenty-one patients with triple oral antidiabetic drug failure and requiring insulin ≥0.4 IU per kg per day with HbA1c <7.5% were randomly assigned to an intervention ( n = 11) and control group ( n = 10) and followed for 12 months. Patients in the intervention group received ABMSCT through a targeted approach, and after 12 weeks, a second dose of stem cells was administered through the antecubital vein after mobilization with G-CSF, while the control group underwent a sham procedure. The primary end point was a reduction in insulin requirement by ≥50% from baseline while maintaining HbA1c <7%. Nine out of the 11 (82%) patients in the intervention group achieved the primary end point, whereas none of the patients in the control group did over the study period ( p = 0.002). The insulin requirement decreased by 66.7% in the intervention group from 42.0 (31.0-64.0) IU per day to 14.0 (0.0-30.0) IU per day ( p = 0.011), while in controls it decreased by 32.1% from 40.5 (31.8-44.3) IU per day to 27.5 (23.5-33.3) IU per day ( p = 0.008) at 12 months. The reduction in insulin requirement was significantly more in the intervention group compared to controls at both 6 ( p = 0.001) and 12 months ( p = 0.004). There was a modest but nonsignificant increase in HbA1c (%) in cases from 6.9% (6.4-7.2%) to 7.1% (6.6-7.5%) as well as in controls from 6.9% (6.2-7.0%) to 7.0% (6.9-7.5%). Ten out of 11 (91%) patients could maintain HbA1c <7% in the intervention group, whereas 6 out of 10 did (60%) in the control group ( p = 0.167). The glucagon-stimulated C-peptide significantly increased in treated cases compared to controls ( p = 0.036). The decrease in insulin requirement positively correlated with stimulated C-peptide ( r = 0.8, p = 0.001). In conclusion, ABMSCT results in a significant decrease in the insulin dose requirement along with an improvement in the stimulated C-peptide levels in T2DM. However, a greater number of patients with a longer duration of follow-up are required to substantiate these observations.
15 March 2018 in American Journal of Neuroradiology
BACKGROUND AND PURPOSE: Stroke is a debilitating illness for which treatment window is limited. Most patients present to the healthcare facility beyond that window. Autologous stem cells have shown some promise for this group of patients. This study was performed to evaluate the safety and the efficacy of intra-arterial infusion of bone marrow–derived mononuclear cells in patients with middle cerebral artery ischemic stroke. MATERIALS AND METHODS: A prospective, randomized, open-label, blinded–end point study was performed from July 2015 to June 2016. Of 229 patients with acute stroke who presented to the hospital during this period, 20 patients who satisfied the inclusion/exclusion criteria were included and randomized into the control and intervention groups. Intra-arterial stem cell infusion into the ipsilateral MCA was performed in the patients in the intervention group at 8–15 days post-stroke ictus. Final analysis at 6 months was performed for primary (safety) and secondary outcomes (efficacy). RESULTS: When we compared the primary end point of the study, no procedure-related mortality, complication, new infarct, or symptomatic intracranial hemorrhage was seen in the intervention group. When we compared the secondary end point of good clinical outcome, 8 (80%) patients in the intervention group showed good clinical outcome (modified Rankin Scale score < 2) with 4 (40%) patients in the control group achieving this (95% confidence interval for good outcome in patients with stem cell infusion, 49.03–94.3, and without stem cell infusion, 16.82–68.73; P = .068). CONCLUSIONS: Intra-arterial infusion of stem cells can be carried out safely in the subacute stage of ischemic stroke. Improved clinical outcomes were observed with intra-arterial stem cell therapy; however, studies with larger cohorts are needed to validate the results.
1 May 2009 in Surgical Neurology
1 January 2019 in Indian Journal Of Ophthalmology
Purpose: This study aims to evaluate normal orbital structures with nonenhanced computed tomography (NCCT) and determine normative data for the Indian population. Methods: CT images of the orbits of 100 patients were retrospectively reviewed on a work station to record the normative data of the orbits. Clinical details of all patients were reviewed to ensure that they did not have ocular/orbital diseases. Both axial and coronal images were utilized to record the data. Results: The mean age of the population evaluated was 34.07 years, with male to female ratio of 1.77. The average orbital index for the left orbit was 97 and for the right side was 103. The mean thickness of left inferior rectus, lateral rectus, medial rectus, and the superior rectus was 3.36 mm, 3.14 mm, 3.80 mm, and 3.75 mm, respectively. The right inferior rectus, lateral rectus, medial rectus, and the superior rectus measured 3.46 mm, 3.14 mm, 3.83 mm, and 3.78 mm, respectively. The optic nerve sheath complex diameter varied between 3.05 mm and 7.17 mm for the left eye and 3.05 mm and 7.0 mm for the right eye. Conclusion: The study provides normative data on various orbital structures in an Indian population. This data is likely to be useful for diagnosing various orbital pathologies and in planning surgical orbital procedures.