Stem Cell Predictive Hemotoxicology

Sim

Neuropathology Appl Neurobio

et al. 2017

Section: Discussionmentioning

confidence: 99%

Distinctive genomic signature of neural and intestinal organoids from familial Parkinson's disease patient‐derived induced pluripotent stem cells

Sim

Neuropathology Appl Neurobio

et al. 2017

“…including neurons, oligodendrocytes and astrocytes . We expected to observe comprehensive neural phenotypes because any changes in the NPC population would ultimately influence all of its progeny cells . NPCs were differentiated under the conventional differentiation conditions and maintained in spherical forms (neurospheres) (Figure A) .…”

Section: Resultsmentioning

confidence: 99%

A novel human model of the neurodegenerative disease GM1 gangliosidosis using induced pluripotent stem cells demonstrates inflammasome activation

The Journal of Pathology

Kwak

Seol

et al. 2015

GM1 gangliosidosis (GM1) is an inherited neurodegenerative disorder caused by mutations in the lysosomal β-galactosidase (β-gal) gene. Insufficient β-gal activity leads to abnormal accumulation of GM1 gangliosides in tissues, particularly in the central nervous system, resulting in progressive neurodegeneration. Here, we report an in vitro human GM1 model, based on induced pluripotent stem cell (iPSC) technology. Neural progenitor cells differentiated from GM1 patient-derived iPSCs (GM1-NPCs) recapitulated the biochemical and molecular phenotypes of GM1, including defective β-gal activity and increased lysosomes. Importantly, the characterization of GM1-NPCs established that GM1 is significantly associated with the activation of inflammasomes, which play a critical role in the pathogenesis of various neurodegenerative diseases. Specific inflammasome inhibitors potently alleviated the disease-related phenotypes of GM1-NPCs in vitro and in vivo. Our data demonstrate that GM1-NPCs are a valuable in vitro human GM1 model and suggest that inflammasome activation is a novel target pathway for GM1 drug development.

Stem Cells Translational Medicine

“…More advance technology has been used recently to test the hypothesis that the quality and potency of primitive stem cell populations can be determined using the TNC fraction in both UCB segments and units. This “null hypothesis” was tested using a standardized and validated [37, 43, 44] ATP bioluminescence stem cell proliferation assay and verified against the CFU assay [45]. The results decisively rejected this hypothesis and instead demonstrated that the mononuclear cell (MNC) fraction, not the TNC fraction, should be used because the latter not only masked but significantly underestimated the presence, quality, and potency of UCB stem cells in both segments and units [45].…”

Section: Current Practices and Perspectivesmentioning

confidence: 99%

“… Difference in stem cell proliferation ability (quality) and potential between the TNC and MNC fractions in a segment and unit from a single umbilical cord blood lot. Primitive hematopoietic stem cells (CFC‐GEMM) are represented by the dotted cell dose‐response linear regression lines, whereas solid lines represent the response of the more primitive lymphohematopoietic stem cells (HPP‐SP) [44, 45]. The quality of the stem cells is provided by the ATP concentration (in micromolars) at any specific cell concentration.…”

Section: Current Practices and Perspectivesmentioning

confidence: 99%

Improving Quality and Potency Testing for Umbilical Cord Blood: A New Perspective

Rich

2015

SUMMARYThis article critically reviews current methods to test and characterize umbilical cord blood (UCB) for hematopoietic stem cell transplantation. These tests include total nucleated cell (TNC) count, viability, viable CD34-positive content, and the colony-forming unit assay. It is assumed that the data obtained are sufficient to perform a UCB stem cell transplant without actually determining the quality and potency of the stem cells responsible for engraftment. This assumption has led not only to a high graft failure rate attributed to low or lack of potency, but also to noncompliance with present statutes that require UCB stem cells to be of high quality and, indeed, potency for a transplant to be successful. New evidence now calls into question the quality of the data, based on the UCB processed TNC fraction because using this impure fraction masks and significantly underestimates the functionality of the stem cells in both the segment and the unit. It is proposed that UCB units should be processed to the mononuclear cell fraction and that new cost-effective technology that measures the quality and potency of UCB stem cells be implemented to achieve better practices in UCB testing. These changes would provide the transplant physician with the assurance that the stem cells will perform as intended and would reduce risk and increase safety and efficacy for the patient. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:967-973 SIGNIFICANCECurrent stem cell transplantation of umbilical cord blood cells requires testing that includes four basic parameters that do not determine whether the stem cells are of high quality, as required by the Stem Cell Therapeutic and Research Act of 2005. No cord blood units collected or transplanted so far have been tested for stem cell quality or potency. New scientific evidence calls into question cord blood processing and testing practices required by regulatory agencies and standards organizations. A new perspective is described that includes stem cell quality and potency testing that could reduce graft failure rates.