Stem Cell Therapy for Neurodegenerative Diseases

Jong Zin Yee; Ki-Wook Oh; Seung Hyun Kim

doi:10.7599/hmr.2015.35.4.229

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Yee, Oh, and Kim: Stem Cell Therapy for Neurodegenerative Diseases

Review

Hanyang Med Rev 2015;35(4):229-235.

Published online: 24 November 2015

DOI: https://doi.org/10.7599/hmr.2015.35.4.229

Stem Cell Therapy for Neurodegenerative Diseases

Jong Zin Yee¹, Ki-Wook Oh^2,³, Seung Hyun Kim^2,³

¹Hanyang University College of Medicine, Seoul, Korea

²Department of Neurology, Hanyang University College of Medicine, Seoul, Korea

³Cell Therapy Center for Neurologic Disorders, Hanyang University Hospital, Seoul, Korea

Correspondence to: Seung Hyun Kim Department of Neurology, Hanyang University College of Medicine, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea Tel: +82-2-2290-8371 Fax: +82-2-2296-8370 E-mail: kimsh1@hanyang.ac.kr

Received 4 September 2015 Revised 6 October 2015 Accepted 13 October 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Neurodegenerative diseases are the hereditary and sporadic conditions which are characterized by progressive neuronal degeneration. Neurodegenerative diseases are emerging as the leading cause of death, disabilities, and a socioeconomic burden due to an increase in life expectancy. There are many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis, but we have no effective treatments or cures to halt the progression of any of these diseases. Stem cell-based therapy has become the alternative option to treat neurodegenerative diseases. There are several types of stem cells utilized; embryonic stem cells, induced pluripotent stem cells, and adult stem cell (mesenchymal stem cells and neural progenitor cells). In this review, we summarize recent advances in the treatments and the limitations of various stem cell technologies. Especially, we focus on clinical trials of stem cell therapies for major neurodegenerative diseases.

Keywords: Neurodegenerative Diseases, Stem Cells, Cell Transplantation

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Table 1.

Stem cell types and sources

	Embryonic stem cell (ESC)	Adult stem cell		Induced pluripotent stem cell (iPSC)
	Embryonic stem cell (ESC)	Mesenchymal stem cell (MSC)	Neural progenitor cell (NPC)	Induced pluripotent stem cell (iPSC)
Cell sources	Inner cell mass of blastocyst	Mesodermal origin tissue (bone marrow, adipose tissue, umbilical cord blood, etc.)	Neural tissue	Skin fibroblast
Differentiation potency	Pluripotent	Multipotent	Unipotent	Pluripotent
Ethical concerns	Destruction of human embryo	No major ethical concerns

Table 2.

Clinical trials for amyotrophic lateral sclerosis

NCT number	Start	Cell Type	Autologous	Location	Phases	Arm	Blind	Funded	Delivery route	Duration of trial
NCT00855400	2007	BM-MNC	Autologous	Spain	I/II	NA	Open label	IIT	Intraspinal with laminectomy T3-4	NA
NCT01984814	2008	BM-MNC	Autologous	India	II	Parallel, retrospective control	Open label	IIT	NA	56 mo
NCT02242071	2008	NA	NA	India	I	Single	Open label	IIT	NA	2 yr
NCT01348451	2009	NSC	Allogeneic spinal cord	USA	I	Single	Open label	SIT	Intraspinal with laminectomy	4 yr
NCT02193893	2010	Progenitor cells	Auto BM	Poland	I	Parallel	Open label	IIT	Intrathecal	1 yr
NCT01082653	2010	NA	Auto BM	USA	I	Single	Open label	SIT	NA	1 yr
NCT01142856	2010	BM-MSC	Autologous	USA	I	Single	Open label	IIT	Intrathecal	2 yr
NCT01254539	2010	BM-MNC	Autologous	Spain	I/II	Two	Double blind	IIT	Intraspinal with laminectomy T3-4 (I), Intrathecal (II)	NA
NCT01363401	2011	BM-MSC	Autologous	Korea	I/II	Parallel	Open label	SIT	Intrathecal	4 mo
NCT01051882	2011	BM-MSC	Autologous	Israel	I/II	Parallel	Open label	SIT	Intramuscular or intrathecal	6 mo
NCT01640067	2011	NSC	NA	Italy	I	Single	Open label	IIT	Intraspinal (lumbar)	At least 3 yr
NCT01494480	2012	UC-MSC	NA	China	II	Single	Open label	IIT	Intrathecal	2 yr
NCT01609283	2012	Ad-MSC	Autologous	USA	I	Single	Open label	IIT	Intrathecal	2 yr
NCT01759797	2012	BM-MSC	NA	Iran	I	Single	Open label	IIT	Intravenous, intraventricular	6 mo
NCT01933321	2012	Hematopoietic stem cells	NA	Mexico	II/III	NA	Open label	IIT	Intrathecal, intravenous	12 mo
NCT01777646	2012	BM-MSC	Autologous	Israel	II	Single	Open label	SIT	Intramuscular and intrathecal	6 mo
NCT01758510	2012	BM-MSC	Allogeneic	Korea	I	Single	Open label	IIT	Intrathecal	6 mo
NCT01730716	2013	NSC	Allogeneic spinal cord	USA	II	Single	Open label	SIT	Intraspinal	2 yr
NCT01771640	2013	BM-MSC	Autologous	Iran	I	Single	Open label	IIT	Intrathecal	6 mo
NCT02116634	2014	MSC	NA	Iran	I/II	NA	Open label	IIT	Intrathecal	2 yr
NCT02017912	2014	BM-MSC	Autologous	USA	II	Parallel	Double blind	SIT	Intramuscular and intrathecal	6 mo
NCT01759784	2014	BM-MSC	NA	Iran	I	Single	Open label	IIT	Intraventricular	NA
NCT02492516	2014	Ad-MSC	Autologous	Iran	I	Single	Open label	IIT	Intravenous	12 mo (safety), 2 mo (function)
NCT02286011	2014	BM-MNC	Autologous	Spain	I	Parallel	Double blind	SIT	Intramuscular	2 yr
NCT02478450	2015	GRP	Allogeneic brain	USA	I/II	Parallel (4 cohort)	Open label, partially blinded	SIT	Intraspinal (cervial and lumbar)	9 mo

Ad, adipose tissue-derived; BM, bone marrow-derived; ESC, embryonic stem cell; GRP, glial-restricted precursor cell; IIT, Investigator Initiated Trial; NA, not available; MNC, mononuclear cells mononuclear cells; MSC, mesenchymal stem cells; NPC, neurogenic progenitor cell; SIT, Sponsor Initiated Trial; UC, umbilical cord-derived.

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