Michael Heke

All Publications

• Type 2 diabetes mellitus duration and obesity alter the efficacy of autologously transplanted bone marrow-derived mesenchymal stem/stromal cells. Stem cells translational medicine Nguyen, L. T., Hoang, D. M., Nguyen, K. T., Bui, D. M., Nguyen, H. T., Le, H. T., Hoang, V. T., Bui, H. T., Dam, P. T., Hoang, X. T., Ngo, A. T., Le, H. M., Phung, N. Y., Vu, D. M., Duong, T. T., Nguyen, T. D., Ha, L. T., Bui, H. T., Nguyen, H. K., Heke, M., Bui, A. V. 2021

  Abstract

  Human bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) represent promising stem cell therapy for the treatment of type 2 diabetes mellitus (T2DM), but the results of autologous BM-MSC administration in T2DM patients are contradictory. The purpose of this study was to test the hypothesis that autologous BM-MSC administration in T2DM patient is safe and that the efficacy of the treatment is dependant on the quality of the autologous BM-MSC population and administration routes. T2DM patients were enrolled, randomly assigned (1:1) by a computer-based system into the intravenous and dorsal pancreatic arterial groups. The safety was assessed in all the treated patients, and the efficacy was evaluated based on the absolute changes in the hemoglobin A1c, fasting blood glucose, and C-peptide levels throughout the 12-month follow-up. Our data indicated that autologous BM-MSC administration was well tolerated in 30 T2DM patients. Short-term therapeutic effects were observed in patients with T2DM duration of <10years and a body mass index <23, which is in line with the phenotypic analysis of the autologous BM-MSC population. T2DM duration directly altered the proliferation rate of BM-MSCs, abrogated the glycolysis and mitochondria respiration of BM-MSCs, and induced the accumulation of mitochondria DNA mutation. Our data suggest that autologous administration of BM-MSCs in the treatment of T2DM should be performed in patients with T2DM duration <10years and no obesity. Prior to further confirming the effects of T2DM on BM-MSC biology, future work with a larger cohort focusing on patients with different T2DM history is needed to understand the mechanism underlying our observation.

  View details for DOI 10.1002/sctm.20-0506

  View details for PubMedID 34080789

• In Reply. Stem cells translational medicine Nguyen Thanh, L., Nguyen, H., Duy Ngo, M., Bui, V. A., Dam, P. T., Thi Phuong Bui, H., Van Ngo, D., Tran, K. T., Thi Thanh Dang, T., Duc Duong, B., Anh Thi Nguyen, P., Forstyth, N., Heke, M. 2021; 10 (6): 827-828

  View details for DOI 10.1002/sctm.20-0452

  View details for PubMedID 34010520

• Outcomes of bone marrow mononuclear cell transplantation combined with interventional education for autism spectrum disorder. Stem cells translational medicine Nguyen Thanh, L., Nguyen, H., Ngo, M. D., Bui, V. A., Dam, P. T., Bui, H. T., Ngo, D. V., Tran, K. T., Dang, T. T., Duong, B. D., Nguyen, P. A., Forsyth, N., Heke, M. 2020

  Abstract

  The aim of this study was to evaluate the safety and efficacy of autologous bone marrow mononuclear cell transplantation combined with educational intervention for children with autism spectrum disorder. An open-label clinical trial was performed from July 2017 to August 2019 at Vinmec International Hospital, Hanoi, Vietnam. Thirty children who fulfilled the autism criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and had Childhood Autism Rating Scale (CARS) scores >37 were selected. Bone marrow was harvested by anterior iliac crest puncture under general anesthesia. The volume collected was as follows: 8 mL/kg for patients under 10 kg (80mL+[body weight in kg-10]*7 mL) for patients above 10 kg. Mononuclear cells were isolated with a Ficoll gradient and then infused intrathecally. The same procedure was repeated 6 months later. After the first transplantation, all patients underwent 8weeks of educational intervention based on the Early Start Denver Model. There were no severe adverse events associated with transplantation. The severity of autism spectrum disorder (ASD) was significantly reduced, with the median CARS score decreasing from 50 (range 40-55.5) to 46.5 (range 33.5-53.5) (P<.05). Adaptive capacity increased, with the median Vineland Adaptive Behavior Scales score rising from 53.5 to 60.5. Social communication, language, and daily skills improved markedly within 18months after transplantation. Conversely, repetitive behaviors and hyperactivity decreased remarkably. Autologous bone marrow mononuclear cell transplantation in combination with behavioral intervention was safe and well tolerated in children with ASD (Trial registration: ClinicalTrials.gov identifier: NCT03225651).

  View details for DOI 10.1002/sctm.20-0102

  View details for PubMedID 32902182

• Outcomes of Bone Marrow-Derived Mononuclear Cell Transplantation for Patients in Persistent Vegetative State After Drowning: Report of Five Cases. Frontiers in pediatrics Liem, N. T., Chinh, V. D., Phuong, D. T., Van Doan, N. n., Forsyth, N. R., Heke, M. n., Thi, P. A., Nguyen, X. H. 2020; 8: 564

  Abstract

  Aim: Anoxic brain injury (ABI) due to non-fatal drowning may cause persistent vegetative state (VS) that is currently incurable. The aim of this paper is to present the safety and feasibility of autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in five drowning children surviving in persistent VS. Methods: We used BMMNC as a novel candidate therapeutic tool in a pilot phase-I study for five patients affected by neurological sequelae after near-death drowning. Autologous BMMNCs were freshly isolated using Ficoll gradient centrifugation then infused intrathecally to five patients. The number of transplantation varied from two to four times depending on the motor function improvement of patient after transplantation. Clinical therapeutic effects were evaluated using gross motor function measure and muscle spasticity rating scales, cognitive assessments, and brain MRI before and after cell administrations. Results: Six months after BMMNC transplantation, no serious complications or adverse events were reported. All five patients displayed improvement across the major parameters of gross motor function, cognition, and muscle spasticity. Three patients displayed improved communication including the expression of words. In particular, one patient remarkably reduced cerebral atrophy, with nearly normal cerebral parenchyma after BMMNC transplantation. Conclusions: Autologous BMMNC transplantation for the treatment of children in persistent VS after drowning is safe, feasible, and can potentially improve motor function and cognition and reduce muscle spasticity. These results pave the way for a future phase II clinical trial to evaluate the efficacy of the therapy.

  View details for DOI 10.3389/fped.2020.00564

  View details for PubMedID 33014944

  View details for PubMedCentralID PMC7511512