Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer's disease dementia: A phase 1 clinical trial

Abstract

IntroductionWe conducted a phase 1 clinical trial in nine patients with mild-to-moderate Alzheimer's disease to evaluate the safety and dose-limiting toxicity of stereotactic brain injection of human umbilical cord blood–derived mesenchymal stem cells (hUCB-MSCs).MethodsThe low- (n = 3) and high-dose (n = 6) groups received a total of 3.0 × 106 cells/60 μL and 6.0 × 106 cells/60 μL, respectively, into the bilateral hippocampi and right precuneus.ResultsNo patient showed serious adverse events including fever during the 24-month follow-up period. During the 12-week follow-up period, the most common acute adverse event was wound pain from the surgical procedure (n = 9), followed by headache (n = 4), dizziness (n = 3), and postoperative delirium (n = 3). There was no dose-limiting toxicity.DiscussionAdministration of hUCB-MSCs into the hippocampus and precuneus by stereotactic injection was feasible, safe, and well tolerated. Further trials are warranted to test the efficacy.Clinical Trial RegistrationClinicalTrial.gov identifier NCT01297218 and NCT01696591.

Immunologic regulatory effects of human umbilical cord blood‐derived mesenchymal stem cells in a murine ovalbumin asthma model

“…[34][35][36][37] Therefore, umbilical cord cells exhibit significant clinical benefits, including their ease of accessibility and regenerative capacities. Therefore, the effect of huMSCs on T cell-mediated immunity was examined by severe acute graft-versus-host disease (www.clinicaltrials.gov).…”

“…severe acute graft-versus-host disease (www.clinicaltrials.gov). [34][35][36][37] Therefore, umbilical cord cells exhibit significant clinical benefits, including their ease of accessibility and regenerative capacities.…”

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

“…[11][12][13] Recently numerous clinical trials have shown that naive human mesenchymal stem cells (MSCs) are safe and beneficial to be considered for design of treatment methods for various pathologies. [14][15][16] The primary mechanism of their therapeutic effects is via secretion of paracrine factors under abnormal and diseased cellular environments. For example, the paracrine action of human MSC has been demonstrated to prevent cell death and induce proliferation of endogenous progenitor cells.…”

Potential of mesenchymal stem cells alone, or in combination, to treat traumatic brain injury

“…The preclinical data on MSCs both alone and in conjunction with other treatment strategies are promising. These cells have entered at least Phase I (safety) clinical trials for multiple nervous system diseases and injuries, most notably cerebral ischemia, multiple sclerosis, Alzheimer's disease, and TBI . While we have a better understanding of the pathologic cascades triggered after TBI and the mechanisms by which MSCs repair the brain and improve functional outcomes, we are still years away from realizing an effective regenerative medicine therapy for TBI that is widely available to patients.…”