Functional recovery of the murine brain ischemia model using human induced pluripotent stem cell-derived telencephalic progenitors

Gomi, Masanori; Takagi, Yasushi; Morizane, Asuka; Doi, Daisuke; Nakagawa, Masaki; Miyamoto, Susumu; Takahashi, J.

doi:10.1016/j.brainres.2012.03.049

Cited by 41 publications

(39 citation statements)

References 35 publications

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“…Mixed results have been obtained when either rodent or human iPSC-derived progenitor cells have been transplanted into stroke-damaged mouse or rat brains. Results ranged from tumor development and the absence of any effects on behavior to significant recovery of function, controllable cell proliferation, and formation of electrophysiologically active synaptic connections (25)(26)(27)(28). Among the reasons for variability are the absence of standard protocols for cell preparation and for modeling stroke and testing treatment outcomes.…”

Section: Testing Ipscs In Animal Disease Modelsmentioning

confidence: 99%

Preclinical Studies for Induced Pluripotent Stem Cell-based Therapeutics

Harding

Mirochnitchenko

2014

Journal of Biological Chemistry

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Induced pluripotent stem cells (iPSCs) and their differentiated derivatives can potentially be applied to cell-based therapy for human diseases. The properties of iPSCs are being studied intensively both to understand the basic biology of pluripotency and cellular differentiation and to solve problems associated with therapeutic applications. Examples of specific preclinical applications summarized briefly in this minireview include the use of iPSCs to treat diseases of the liver, nervous system, eye, and heart and metabolic conditions such as diabetes. Early stage studies illustrate the potential of iPSC-derived cells and have identified several challenges that must be addressed before moving to clinical trials. These include rigorous quality control and efficient production of required cell populations, improvement of cell survival and engraftment, and development of technologies to monitor transplanted cell behavior for extended periods of time. Problems related to immune rejection, genetic instability, and tumorigenicity must be solved. Testing the efficacy of iPSC-based therapies requires further improvement of animal models precisely recapitulating human disease conditions. The breakthrough discovery that specific sets of transcription factors can reprogram cell fate and generate induced pluripotent stem cells (iPSCs) 2 from various cell types has opened many new possibilities for research on cell states, differentiation, pluripotency, and general cell identity but, most importantly, has catalyzed the development of a whole new field of regenerative medicine (1). The field is still in a relatively early stage regarding a clear understanding of underlying developmental processes, cell behavior, and biological effects after cellgrafting experiments. The use of iPSCs and their products for human applications poses many new challenges from the experimental and regulatory points of view due to the unique properties of the cells and novel mechanism of their action.

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Section: Testing Ipscs In Animal Disease Modelsmentioning

confidence: 99%

Preclinical Studies for Induced Pluripotent Stem Cell-based Therapeutics

Harding

Mirochnitchenko

2014

Journal of Biological Chemistry

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“…Preclinical stroke studies have confirmed the ability of iPSC-derived NSCs to enhance stroke recovery following IC delivery [44][45][46][47], including in neonatal stroke [48], and have further shown that iPSC-derived NSCs can differentiate into multiple types of functionally active neurons following IC delivery into the stroke-injured brain [45,46]. Similar to embryonic-derived NSCs, the potential to form tumors or ectopic tissue by iPSC-derived NSCs remains a concern, prompting development of methods to generate induced NSCs (iNSCs) or induced neuronal (iN) cells directly from somatic cells without initial reversion to a pluripotent state [49,50].…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 96%

Neural Stem Cells in Stroke: Intracerebral Approaches

Manley

Azevedo-Pereira

Bliss

et al. 2015

Cell Therapy for Brain Injury

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“…Early research also included undifferentiated pluripotent stem cells, however, their use has become limited due to the risk of teratoma and tumor formation (Kawai et al, 2010;Yamashita et al, 2011). Transplanted cells have been demonstrated to promote stroke recovery in animal models through a variety of mechanisms: stimulating both endogenous NPCs and endothelial progenitor cells to migrate to ischemic sites (Bliss et al, 2010;Lindvall and Kokaia, 2011;Dailey et al, 2013), stimulating the proliferation of neuroblasts in the SVZ (Chen et al, 2003;Jin et al, 2011a;Zhang et al, 2011), promoting angiogenesis in the peri-infarct zone (Horie et al, 2011;Zhang et al, 2011;Oki et al, 2012), and decreasing infarct size (Chen et al, 2010a;Gomi et al, 2012;Oki et al, 2012). In addition to the effects on endogenous tissue, transplanted cells can integrate into the existing neural circuitry, reestablishing connections with host cells ; however, it remains unclear if these new connections contribute directly to recovery.…”

Section: Cell Delivery Goals Of Cell Therapymentioning

confidence: 99%