Prospect of cell therapy for Parkinson's disease

Pawitan, Jeanne Adiwinata

doi:10.5115/acb.2011.44.4.256

Cited by 13 publications

(12 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Replacement therapy, which uses the human fetal mesencephalon transplanted into the brain, showed some symptomatic relief (Freed et al,2001; Mendez et al,2008). However, this strategy using the human fetal mesencephalon involves ethical issues and problems in obtaining adequate numbers of DA neurons (Dunnett and Björkland,1999; Freed,2002; Pawitan,2011; Politis and Lindvall,2012).…”

mentioning

confidence: 99%

Therapeutic effects of human mesenchymal and hematopoietic stem cells on rotenone‐treated parkinsonian mice

Inden

Takata

Nishimura

et al. 2012

J of Neuroscience Research

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

Therapeutic effects of human mesenchymal and hematopoietic stem cells on rotenone‐treated parkinsonian mice

Inden

Takata

Nishimura

et al. 2012

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…Several neurotrophic factors, such as nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor (GDNF), and/or those neurotrophic factors-secreting cell implants enhance function and survival of transplanted cells as well as remaining DA neurons in PD models [23], [24], [25], [26], [27]. Among these trophic factors, striatal expression of GDNF was examined, because it exerts neurotrophic and neuroprotective effects on DA neurons.…”

Section: Discussionmentioning

confidence: 99%

“…However, those cell transplantation therapies have several possible adverse effects such as off-state dyskinesia, immune rejection and immunosuppressant use in allogeneic implants and tumor formation in stem cell implants [25], [28]. Furthermore, transplantation of fetal cells or embryonic stem cells has ethical and social concerns.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of Melanocytes Obtained from the Skin Ameliorates Apomorphine-Induced Abnormal Behavior in Rodent Hemi-Parkinsonian Models

et al. 2013

View full text Add to dashboard Cite

Tyrosinase, which catalyzes both the hydroxylation of tyrosine and consequent oxidation of L-DOPA to form melanin in melanocytes, is also expressed in the brain, and oxidizes L-DOPA and dopamine. Replacement of dopamine synthesis by tyrosinase was reported in tyrosine hydroxylase null mice. To examine the potential benefits of autograft cell transplantation for patients with Parkinson’s disease, tyrosinase-producing cells including melanocytes, were transplanted into the striatum of hemi-parkinsonian model rats or mice lesioned with 6-hydroxydopamine. Marked improvement in apomorphine-induced rotation was noted at day 40 after intrastriatal melanoma cell transplantation. Transplantation of tyrosinase cDNA-transfected hepatoma cells, which constitutively produce L-DOPA, resulted in marked amelioration of the asymmetric apomorphine-induced rotation in hemi-parkinsonian mice and the effect was present up to 2 months. Moreover, parkinsonian mice transplanted with melanocytes from the back skin of black newborn mice, but not from albino mice, showed marked improvement in the apomorphine-induced rotation behavior up to 3 months after the transplantation. Dopamine-positive signals were seen around the surviving transplants in these experiments. Taken together with previous studies showing dopamine synthesis and metabolism by tyrosinase, these results highlight therapeutic potential of intrastriatal autograft cell transplantation of melanocytes in patients with Parkinson’s disease.

show abstract

“…The major obstacle lies in the difficulty to obtain human fetal tissue. To improve cell therapy approach used in clinic, PSCs including ESCs and iPSCs could serve as excellent cellular sources to produce dopaminergic neurons (Pawitan, 2011). hESC-derived midbrain dopamine neurons have been successfully transplanted into PD patients’ brains and some favorable results were achieved in cell replacement trials (Bjorklund et al, 2002; Kim et al, 2002; Wernig et al, 2004; Roy et al, 2006; Sanchez-Pernaute et al, 2008; Yang et al, 2008; Kriks et al, 2011).…”

Section: Cn and Pdmentioning

confidence: 99%