scholarly journals Generation of Induced Pluripotent Stem Cells and Neural Stem/Progenitor Cells from Newborns with Spina Bifida Aperta

2017 ◽  
Vol 11 (6) ◽  
pp. 870-879 ◽  
Author(s):  
Yohei Bamba ◽  
Masahiro Nonaka ◽  
Natsu Sasaki ◽  
Tomoko Shofuda ◽  
Daisuke Kanematsu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Spina Bifida ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Clinical Use ◽  
Spina Bifida Aperta ◽  
Neural Stem Progenitor Cells ◽  
Induced Pluripotent

<sec><title>Study Design</title><p>We established induced pluripotent stem cells (iPSCs) and neural stem/progenitor cells (NSPCs) from three newborns with spina bifida aperta (SBa) using clinically practical methods.</p></sec><sec><title>Purpose</title><p>We aimed to develop stem cell lines derived from newborns with SBa for future therapeutic use.</p></sec><sec><title>Overview of Literature</title><p>SBa is a common congenital spinal cord abnormality that causes defects in neurological and urological functions. Stem cell transplantation therapies are predicted to provide beneficial effects for patients with SBa. However, the availability of appropriate cell sources is inadequate for clinical use because of their limited accessibility and expandability, as well as ethical issues.</p></sec><sec><title>Methods</title><p>Fibroblast cultures were established from small fragments of skin obtained from newborns with SBa during SBa repair surgery. The cultured cells were transfected with episomal plasmid vectors encoding reprogramming factors necessary for generating iPSCs. These cells were then differentiated into NSPCs by chemical compound treatment, and NSPCs were expanded using neurosphere technology.</p></sec><sec><title>Results</title><p>We successfully generated iPSC lines from the neonatal dermal fibroblasts of three newborns with SBa. We confirmed that these lines exhibited the characteristics of human pluripotent stem cells. We successfully generated NSPCs from all SBa newborn-derived iPSCs with a combination of neural induction and neurosphere technology.</p></sec><sec><title>Conclusions</title><p>We successfully generated iPSCs and iPSC-NSPCs from surgical samples obtained from newborns with SBa with the goal of future clinical use in patients with SBa.</p></sec>

scholarly journals Small-scale screening of anticancer drugs acting specifically on neural stem/progenitor cells derived from human-induced pluripotent stem cells using a time-course cytotoxicity test

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4187 ◽  
Author(s):  
Hayato Fukusumi ◽  
Yukako Handa ◽  
Tomoko Shofuda ◽  
Yonehiro Kanemura
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Anticancer Drugs ◽  
Pluripotent Stem Cells ◽  
Time Course ◽  
Neural Stem Progenitor Cells ◽  
Induced Pluripotent

Since the development of human-induced pluripotent stem cells (hiPSCs), various types of hiPSC-derived cells have been established for regenerative medicine and drug development. Neural stem/progenitor cells (NSPCs) derived from hiPSCs (hiPSC-NSPCs) have shown benefits for regenerative therapy of the central nervous system. However, owing to their intrinsic proliferative potential, therapies using transplanted hiPSC-NSPCs carry an inherent risk of undesired growth in vivo. Therefore, it is important to find cytotoxic drugs that can specifically target overproliferative transplanted hiPSC-NSPCs without damaging the intrinsic in vivo stem-cell system. Here, we examined the chemosensitivity of hiPSC-NSPCs and human neural tissue—derived NSPCs (hN-NSPCs) to the general anticancer drugs cisplatin, etoposide, mercaptopurine, and methotrexate. A time-course analysis of neurospheres in a microsphere array identified cisplatin and etoposide as fast-acting drugs, and mercaptopurine and methotrexate as slow-acting drugs. Notably, the slow-acting drugs were eventually cytotoxic to hiPSC-NSPCs but not to hN-NSPCs, a phenomenon not evident in the conventional endpoint assay on day 2 of treatment. Our results indicate that slow-acting drugs can distinguish hiPSC-NSPCs from hN-NSPCs and may provide an effective backup safety measure in stem-cell transplant therapies.

scholarly journals Potential of cardiac stem/progenitor cells and induced pluripotent stem cells for cardiac repair in ischaemic heart disease

2013 ◽  
Vol 125 (7) ◽  
pp. 319-327 ◽  
Author(s):  
Wei Eric Wang ◽  
Xiongwen Chen ◽  
Steven R. Houser ◽  
Chunyu Zeng
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Heart Disease ◽  
Cell Therapy ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Autologous Transplantation ◽  
Cardiac Repair ◽  
Induced Pluripotent

Stem cell therapy has emerged as a promising strategy for cardiac and vascular repair. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. CS/PCs (cardiac stem/progenitor cells) are one type of adult stem cell with the potential to differentiate into cardiac lineages (cardiomyocytes, smooth muscle cells and endothelial cells). iPSCs (induced pluripotent stem cells) also have the capacity to differentiate into necessary cells to rebuild injured cardiac tissue. Both types of stem cells have brought promise for cardiac repair. The present review summarizes recent advances in cardiac cell therapy based on these two cell sources and discusses the advantages and limitations of each candidate. We conclude that, although both types of stem cells can be considered for autologous transplantation with promising outcomes in animal models, CS/PCs have advanced more in their clinical application because iPSCs and their derivatives possess inherent obstacles for clinical use. Further studies are needed to move cell therapy forward for the treatment of heart disease.

Efficient Induction of CD34+ Progenitor Cells From Human Bone Marrow Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells with Defined Chemicals

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2347-2347
Author(s):  
Yulin Xu ◽  
Lizhen Liu ◽  
Shan Fu ◽  
Lifei Zhang ◽  
Yongxian Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Endothelial Cell ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Clinical Application ◽  
Pluripotent Stem Cells ◽  
Cell Potential ◽  
Efficient Induction ◽  
Induced Pluripotent

Abstract Abstract 2347 Induced pluripotent stem cells (iPSCs) hold great potential in clinical application with indefinite passages, pluripotency of forming three germ layers and immunological compatibility with patients. Human bone marrow mesenchymal stem cell-derived iPSCs (hBMMSC-iPSCs) may have more virtues than other types of cell–derived iPSCs do in diseases treatment for their wide application in clinic for many years. Efficient differentiation of induced pluripotent stem cells (iPSCs) to a specialized cell type is a crucial step for iPSC clinical application. CD34+ progenitor cells derived from hBMMSC-iPSCs by treatment with defined chemicals have not been reported. Here, base on the efficient generation of hBMMSC-iPSCs with cDNA encoding four transcription factors OCT4, SOX2, KLF4 and c-MYC, and the compounds of p53 siRNA, VPA and Vc, we proposed that CD34+ progenitor cells, retaining hematopoietic and endothelial cell potential, could be efficiently obtained from hBMMSC-iPSCs by treatments with chemicals exerting function on mesoderm and hematopoietic cells. The differentiated hBMMSC-iPSCs treated with the chemicals comprised nearly 20% proportion of CD34+ progenitor cells, about 20-fold increasing compared to the spontaneous differentiation hBMMSC-iPSCs and higher than that from human skin fibroblast-derived iPSCs (hFib-iPSCs) (nearly 15%) and human embryonic stem cell line H1 (nearly 17%) by flow cytometry analysis. Those cells retained the hematopoietic and endothelial cell potential as CD34+ progenitor cells derived from umbilical cord blood. After coculture with the first chemical cocktails including BMP4 and SCF for 5 days, a higher proportion of the mesoderm cells were induced from hBMMSC-iPSCs than that from the untreated groups (P<0.05) by analysis the expression of Brachyury and GATA2 with RT-PCR and immunochemistry analysis. The efficient mesoderm cell activity was then directed to CD34+ progenitor cells with the following chemicals as SCF and IL-3 for another 7–9 days by analysis of cellular phenotype and the expression of the hematopoietic transcription factors TAL-1 and GATA-2. Sorted by CD34 magnetic separation and exposed to semisolid media with the hematopoietic cytokines including EPO and G-CSF, CD34+ progenitor cells formed various hematopoietic colonies as BFU-E, CFU-E, CFU-G, CFU-GM, and CFU-GEMM. CFUs derived from hBMMSC-iPSC groups treated with the chemicals outnumbered those from hFib-iPSCs, the spontaneous differentiation hBMMSC-iPSCs and H1 groups. Hematopoietic cell lineages as erythroid, granulocyte, and megakaryocyte were identified with Wright-Giemsa staining. During the hematopoietic commitment of hBMMSC-iPSCs, the pluripotent gene Oct4 continued to be down-regulated and completely vanished at day 14 after the induction. However, the expression of the hematologic transcription factor GATA-2 experienced a dynamic process with up-regulation at the initial induction stage and then gradual down-regulation after CD34+ progenitor cell commitment to CFU forming. Endothelial cell potential of CD34+ progenitor cells was also verified by demonstration of the vascular tube-like structure formation and the expression of endothelial specific markers CD31 and VE-CADHERIN. The efficient induction of CD34+ progenitor cells from hBMMSC-iPSCs with defined chemicals, avoiding contamination from indentified factors with using mouse feeder lays or other poorly defined induction components, gives an opportunity for the generation of unlimited HLA matched transplantable cells, provides cell models for study the mechanism of haemopoiesis and related diseases, and therefore promotes iPSC clinical application. Disclosures: No relevant conflicts of interest to declare.

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