Therapeutic effects of human mesenchymal and hematopoietic stem cells on rotenone-treated parkinsonian mice.
To appreciate the potential applications of stem cell technology in neurodegenerative diseases, including Parkinson's disease (PD), it is important to understand the characteristics of the various types of stem cells. In this study, we designed a set of experiments to compare the ability of three types of human stem cells--mesenchymal stem cells (MSCs), bone marrow CD34(+) cells (BM), and cord blood CD34(+) cells (CB)--using rotenone-treated NOD/SCID mice. Rotenone was orally administered once daily at a dose of 30 mg/kg for 56 days to induce a parkinsonian phenotype. Intravenous delivery of CB into rotenone-treated mice was slightly more beneficial than that of MSCs or BM according to both histological and behavioral analyses. Human nucleus (hNu)(+) cells, which are a specific marker of human cells, were observed in the striatum of rotenone-treated mice transplanted with stem cells. These hNu(+) cells expressed tyrosine hydroxylase (TH). Additionally, α-synuclein(+)/TH(+) cells in the substantia nigra pars compacta decreased significantly following stem cell transplantation. Immunohistochemical analysis also revealed that chronic exposure to rotenone decreased glial cell line-derived neurotrophic factor immunoreactivity and that the reduction was improved by each stem cell transplantation. Gene expression analyses revealed that MSCs, BM, and CB expressed several neurotrophic factors. These results suggest that the beneficial effects of intravenous delivery of stem cells into rotenone-treated mice may result not only from a neurotrophic effect but also from endogenous brain repair mechanisms and the potential of intravenous delivery of stem cells derived from an autologous source for clinical applications in PD.
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan.
Masatoshi
M
Inden
Kazuyuki
K
Takata
Kaneyasu
K
Nishimura
Yoshihisa
Y
Kitamura
Eishi
E
Ashihara
Kanji
K
Yoshimoto
Hiroyoshi
H
Ariga
Osamu
O
Honmou
Shun
S
Shimohama
D000818:Animals; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009414:Nerve Growth Factors / Q000096:biosynthesis; D020734:Parkinsonian Disorders / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012402:Rotenone / Q000633:toxicity; D014475:Uncoupling Agents / Q000633:toxicity
D009414:Nerve Growth Factors; D014475:Uncoupling Agents; D012402:Rotenone