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Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia.
Stem Cell Res Ther 2011; 2(5):38SC

Abstract

INTRODUCTION

Stem cell transplantation is a promising therapeutic strategy for the treatment of stroke. Mesenchymal stem cells (MSCs) are a potential cell source for clinical application because they can be easily obtained and cultivated with a high proliferative capacity. The safety and efficacy of cell therapy depends on the mode of cell administration. To determine the therapeutic potential of intrathecal administration of MSCs by lumbar puncture (LP), we administrated human umbilical cord blood-derived MSCs (hUCB-MSCs) intrathecally into the lumbar spinal cord or intravenously into the tail vein in a rat model of stroke, and then investigated whether hUCB-MSCs could enter the brain, survive, and improve post-stroke neurological functional recovery.

METHODS

hUCB-MSCs (1.0 × 10(6)) were administrated three days after stroke induced by occlusion of the middle cerebral artery. The presence of hUCB-MSCs and their survival and differentiation in the brain tissue of the rats was examined by immunohistochemistry. Recovery of coordination of movement after administration of hUCB-MSCs was examined using a Rotarod test and adhesive-removal test on the 7th, 14th, 21st, and 28th days after ischemia. The volume of ischemic lesions seven days after the experimental procedure was evaluated using 2-3-5-triphenyltetrazolium (TTC) staining.

RESULTS

Rats receiving hUCB-MSCs intrathecally by LP had a significantly higher number of migrated cells within the ischemic area when compared with animals receiving cells intravenously. In addition, many of the cells administered intrathecally survived and a subset of them expressed mature neural-lineage markers, including the mature neuron marker NeuN and glial fibrillary acidic protein, typical of astrocytes. Animals that received hUCB-MSCs had significantly improved motor function and reduced ischemic damage when compared with untreated control animals. Regardless of the administration route, the group treated with 1 × 10(6) hUCB-MSCs showed better neurological recovery, without significant differences between the two treatment groups. Importantly, intrathecal administration of 5 × 10(5) hUCB-MSCs significantly reduced ischemic damage, but not in the intravenously treated group. Furthermore, the cells administered intrathecally survived and migrated into the ischemic area more extensively, and differentiated significantly into neurons and astrocytes.

CONCLUSIONS

Together, these results indicate that intrathecal administration of MSCs by LP may be useful and feasible for MSCs treatment of brain injuries, such as stroke, or neurodegenerative disorders.

Authors+Show Affiliations

Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21939558

Citation

Lim, Jung Yeon, et al. "Therapeutic Effects of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells After Intrathecal Administration By Lumbar Puncture in a Rat Model of Cerebral Ischemia." Stem Cell Research & Therapy, vol. 2, no. 5, 2011, p. 38.
Lim JY, Jeong CH, Jun JA, et al. Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia. Stem Cell Res Ther. 2011;2(5):38.
Lim, J. Y., Jeong, C. H., Jun, J. A., Kim, S. M., Ryu, C. H., Hou, Y., ... Jeun, S. S. (2011). Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia. Stem Cell Research & Therapy, 2(5), p. 38. doi:10.1186/scrt79.
Lim JY, et al. Therapeutic Effects of Human Umbilical Cord Blood-derived Mesenchymal Stem Cells After Intrathecal Administration By Lumbar Puncture in a Rat Model of Cerebral Ischemia. Stem Cell Res Ther. 2011 Sep 22;2(5):38. PubMed PMID: 21939558.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia. AU - Lim,Jung Yeon, AU - Jeong,Chang Hyun, AU - Jun,Jin Ae, AU - Kim,Seong Muk, AU - Ryu,Chung Heon, AU - Hou,Yun, AU - Oh,Wonil, AU - Chang,Jong Wook, AU - Jeun,Sin-Soo, Y1 - 2011/09/22/ PY - 2011/04/08/received PY - 2011/09/22/accepted PY - 2011/9/24/entrez PY - 2011/9/24/pubmed PY - 2012/10/4/medline SP - 38 EP - 38 JF - Stem cell research & therapy JO - Stem Cell Res Ther VL - 2 IS - 5 N2 - INTRODUCTION: Stem cell transplantation is a promising therapeutic strategy for the treatment of stroke. Mesenchymal stem cells (MSCs) are a potential cell source for clinical application because they can be easily obtained and cultivated with a high proliferative capacity. The safety and efficacy of cell therapy depends on the mode of cell administration. To determine the therapeutic potential of intrathecal administration of MSCs by lumbar puncture (LP), we administrated human umbilical cord blood-derived MSCs (hUCB-MSCs) intrathecally into the lumbar spinal cord or intravenously into the tail vein in a rat model of stroke, and then investigated whether hUCB-MSCs could enter the brain, survive, and improve post-stroke neurological functional recovery. METHODS: hUCB-MSCs (1.0 × 10(6)) were administrated three days after stroke induced by occlusion of the middle cerebral artery. The presence of hUCB-MSCs and their survival and differentiation in the brain tissue of the rats was examined by immunohistochemistry. Recovery of coordination of movement after administration of hUCB-MSCs was examined using a Rotarod test and adhesive-removal test on the 7th, 14th, 21st, and 28th days after ischemia. The volume of ischemic lesions seven days after the experimental procedure was evaluated using 2-3-5-triphenyltetrazolium (TTC) staining. RESULTS: Rats receiving hUCB-MSCs intrathecally by LP had a significantly higher number of migrated cells within the ischemic area when compared with animals receiving cells intravenously. In addition, many of the cells administered intrathecally survived and a subset of them expressed mature neural-lineage markers, including the mature neuron marker NeuN and glial fibrillary acidic protein, typical of astrocytes. Animals that received hUCB-MSCs had significantly improved motor function and reduced ischemic damage when compared with untreated control animals. Regardless of the administration route, the group treated with 1 × 10(6) hUCB-MSCs showed better neurological recovery, without significant differences between the two treatment groups. Importantly, intrathecal administration of 5 × 10(5) hUCB-MSCs significantly reduced ischemic damage, but not in the intravenously treated group. Furthermore, the cells administered intrathecally survived and migrated into the ischemic area more extensively, and differentiated significantly into neurons and astrocytes. CONCLUSIONS: Together, these results indicate that intrathecal administration of MSCs by LP may be useful and feasible for MSCs treatment of brain injuries, such as stroke, or neurodegenerative disorders. SN - 1757-6512 UR - https://www.unboundmedicine.com/medline/citation/21939558/Therapeutic_effects_of_human_umbilical_cord_blood_derived_mesenchymal_stem_cells_after_intrathecal_administration_by_lumbar_puncture_in_a_rat_model_of_cerebral_ischemia_ L2 - https://stemcellres.biomedcentral.com/articles/10.1186/scrt79 DB - PRIME DP - Unbound Medicine ER -