Comparative study of efficacy of dopaminergic neuron differentiation between embryonic stem cell and protein-based induced pluripotent stem cell.
In patients with Parkinson's disease (PD), stem cells can serve as therapeutic agents to restore or regenerate injured nervous system. Here, we differentiated two types of stem cells; mouse embryonic stem cells (mESCs) and protein-based iPS cells (P-iPSCs) generated by non-viral methods, into midbrain dopaminergic (mDA) neurons, and then compared the efficiency of DA neuron differentiation from these two cell types. In the undifferentiated stage, P-iPSCs expressed pluripotency markers as ES cells did, indicating that protein-based reprogramming was stable and authentic. While both stem cell types were differentiated to the terminally-matured mDA neurons, P-iPSCs showed higher DA neuron-specific markers' expression than ES cells. To investigate the mechanism of the superior induction capacity of DA neurons observed in P-iPSCs compared to ES cells, we analyzed histone modifications by genome-wide ChIP sequencing analysis and their corresponding microarray results between two cell types. We found that Wnt signaling was up-regulated, while SFRP1, a counter-acting molecule of Wnt, was more suppressed in P-iPSCs than in mESCs. In PD rat model, transplantation of neural precursor cells derived from both cell types showed improved function. The present study demonstrates that P-iPSCs could be a suitable cell source to provide patient-specific therapy for PD without ethical problems or rejection issues.
National Research Laboratory for Stem Cell Niche, Seoul National University Hospital, Seoul, Korea ; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
Yoo-Wook
YW
Kwon
National Research Laboratory for Stem Cell Niche, Seoul National University Hospital, Seoul, Korea ; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
Yeon-Ju
YJ
Chung
National Research Laboratory for Stem Cell Niche, Seoul National University Hospital, Seoul, Korea ; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
Joonoh
J
Kim
National Research Laboratory for Stem Cell Niche, Seoul National University Hospital, Seoul, Korea ; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea.
Ho-Jae
HJ
Lee
Division of Molecular and Life Sciences,Pohang University of Science and Technology, Pohang, Korea.
Jihwan
J
Park
Division of Molecular and Life Sciences,Pohang University of Science and Technology, Pohang, Korea.
Tae-Young
TY
Roh
National Research Laboratory for Stem Cell Niche, Seoul National University Hospital, Seoul, Korea ; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea ; Department of Internal Medicine, Seoul National University, Seoul, Korea.
Hyun-Jai
HJ
Cho
Cardiovascular center, Seoul National University Bundang Hospital, Seoul National University, Seoul, Korea.
Chang-Hwan
CH
Yoon
Department of Internal Medicine, Seoul National University, Seoul, Korea.
Bon-Kwon
BK
Koo
National Research Laboratory for Stem Cell Niche, Seoul National University Hospital, Seoul, Korea ; Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Korea ; Department of Internal Medicine, Seoul National University, Seoul, Korea ; Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, Korea.
Hyo-Soo
HS
Kim
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000601:surgery; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein; D000094742:Secreted Frizzled-Related Proteins
D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016627:Oxidopamine; D011506:Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C438615:Wnt5a protein, mouse