Poststroke Intravenous Transplantation of Human Mesenchymal Stem Cells Improves Brain Repair Dynamics and Functional Outcomes in Aged Mice.

Autor:	Zhang W; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.).; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., F.Z., J.C.)., Pu H; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.).; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., F.Z., J.C.)., Hu X; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.).; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., F.Z., J.C.)., Shi Y; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.).; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., F.Z., J.C.)., Leak RK; Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA (R.K.L.)., Anne Stetler R; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.).; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., F.Z., J.C.)., Ye Q; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.).; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., F.Z., J.C.)., Lyu J; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.)., Zhang F; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.).; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., F.Z., J.C.)., Wechsler LR; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (L.R.W.)., Chen J; Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., J.L., F.Z., J.C.).; Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, PA (W.Z., H.P., X.H., Y.S., R.A.S., Q.Y., F.Z., J.C.).
Jazyk:	angličtina
Zdroj:	Stroke [Stroke] 2023 Apr; Vol. 54 (4), pp. 1088-1098. Date of Electronic Publication: 2023 Mar 13.
DOI:	10.1161/STROKEAHA.122.041507
Abstrakt:	Background: Stroke is the primary cause of chronic disability in the elderly, as there are no neurorestorative treatments for those who do not qualify for recanalization therapy. Experimental evidence in stroke animals suggests that transplantation of bone marrow-derived human mesenchymal stem cells (hMSCs) holds promise, but hMSC transplantation has not been systematically tested in aged animals. We tested the hypothesis that poststroke hMSC transplantation improves stroke recovery in aged mice by promoting brain repair. Methods: Permanent focal cerebral ischemia was induced in 20-month-old C57BL/6 male mice by distal middle cerebral artery occlusion. Bone marrow-derived hMSCs were expanded in vitro and then administrated intravenously into mice (1×10 6 cells in PBS) 24 hours after distal middle cerebral artery occlusion. Sensorimotor and cognitive functions, brain atrophy, and brain repair processes (neurogenesis, angiogenesis, oligodendrogenesis) were assessed for up to 56 days after stroke. Results: Poststroke hMSC transplantation did not mitigate brain atrophy or improve neuronal survival at 56 days after distal middle cerebral artery occlusion. However, hMSC-treated mice displayed superior neurobehavioral performances in the open field, rotarod, adhesive removal, novel object, and Morris water maze tests compared with PBS-treated controls. hMSCs promoted white matter integrity and enhanced angiogenesis and oligodendrogenesis-but not neurogenesis-in the stroke brain. Positive correlations between neurobehavioral performance and brain repair profiles or white matter integrity were observed in stroke mice. Conclusions: Poststroke hMSC transplantation improves long-term stroke recovery in aged mice, likely via mechanisms involving enhanced microvascular regeneration and white matter restoration.
Databáze:	MEDLINE
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