Cell therapy for cerebral hemorrhage: Five year follow-up report

Abstract

The aim of the study was to examine treatment of cerebral hemorrhages with bone-marrow or human umbilical cord-derived mesenchymal stem cells (BMSCs or Hu-MSCs) and conventional surgical approaches, and determine and compare the effectiveness, feasibility, safety and reproducibility of each method. A retrospective analysis was performed on a cohort of cell-treated cerebral hemorrhage patients from October 1, 2007 to October 1, 2009. A total of 24 patients, all of whom received conventional surgical treatment, were classified as follows: i) The control group consisted of 8 patients who received only hematoma removal surgery, ii) the autologous group consisted of 7 patients who received additional autologous bone marrow mononuclear cell transplantation, and iii) the allograft group consisted of 9 patients who received additional umbilical cord mononuclear cell transplantation. After conventional hematoma removal surgery and X-ray supervision within 24 h and at 7 days, neurological disability and function tests were completed 3, 6, 12, 36 and 60 months later. The T-cell marker plasma levels were analyzed after 60 months. The results showed that, at approximately 3.5 months after graft the hematomas in all the groups were completely reabsorbed as observed on computed tomography scans. However, the functional outcomes in the cell-transplanted groups were better than in the control group after 5 years. While the National Institutes of Health Stroke Scale, modified Rankin score and modified Barthel index scores were simliar in the cell-transplanted groups, patients in the allograft group had better outcomes than those in the autologous graft group starting at 3 months and until the end of the follow-up period. The serum levels of T-cell markers CD4, CD56 and human leukocyte antigen-DR in the allograft group showed no signs of immunogenic graft complications and there were no significant differences in T-cell subtypes among the patient groups. The results of the present study suggest that, treatment of cerebral hemorrhage patients can be safely and effectively accomplished using Hu-MSC grafting and larger clinical trials should be considered in the future.

Mesenchymal stem cells for hemorrhagic stroke: status of preclinical and clinical research

“…72–77 As with preclinical research, a range of sources was used to obtain MSCs. Bone marrow-derived MSCs, 73,74,77 and umbilical cord-derived MSCs 72,74,75 were the most often used in clinical trials. Bone marrow-derived mononuclear cells containing MSCs were also used, 76 and combination cell transplantation of olfactory ensheathing cells (OEC), neural progenitor cells (NPC), UC-MSCs, and Schwann cells (SCs) were tested.…”

“…In the five published cases of MSC treatment for hemorrhagic stroke that measured functional outcomes, four groups reported improvements in these measures relative to the control groups, which is in contrast to the original Bhasin 73 article, as well as improvements in other measures such as speech, breathing, and pain reporting. 74–77 Moreover, computed tomography (CT) scans purportedly demonstrate accelerated hematoma reabsorption by 2 weeks after MSC transplantation in patients, however no statistical testing was performed to support this. 74 These functional effects were reported from 6 months to 5 years after MSC treatment, regardless of MSC source, dose, administration route or timing of treatment.…”

Outcomes of Bone Marrow-Derived Mononuclear Cell Transplantation for Patients in Persistent Vegetative State After Drowning: Report of Five Cases

“…There has been growing evidence of safety and benefit of autologous bone marrow-derived mononuclear cells (BMMNCs) in patients with a variety of neurological damage conditions (8)(9)(10)(11)(12)(13)(14). BMMNCs are a heterogeneous group of cells consisting of a small proportion of progenitor cells, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), MUSE cells, and endothelial progenitor cells that could potentially produce synergic effect promoting neuronal protection and regeneration and functional recovery.…”

“…In humans, we and others recently demonstrated the safety and feasibility of BMMNC transplantation in patients with a variety of neurological damage conditions such as traumatic brain injury ( 29 , 30 ), cerebral hemorrhage ( 9 ), stroke ( 31 – 34 ), spinal cord injury ( 10 , 11 ), cerebral palsy ( 12 ), and autism ( 13 , 14 ). These encouraging results in combination with the neuroplasticity of the childhood brain provide a great opportunity for the stem cell-based treatment of pediatric non-fatal drowning ABI.…”

Late Intrathecal Cell Therapy Increases Brain Glucose Metabolism and Improves the Long-Term Established Sequelae of Cerebral Hemorrhage

“…After numerous preclinical studies and a growing experience in patients, there seems to be evidence of the usefulness of cell therapy in stroke, improving functional recovery [1][2][3]. However, these studies have generally been performed in acute phases, and the benefit has been attributed to the well-known properties of cell therapy, achieving neuroprotective effect or enhancing endogenous neurogenesis.…”