Back to Search
Start Over
Chemotherapy-Induced Neuropathy and Drug Discovery Platform Using Human Sensory Neurons Converted Directly from Adult Peripheral Blood.
- Source :
-
Stem cells translational medicine [Stem Cells Transl Med] 2019 Nov; Vol. 8 (11), pp. 1180-1191. Date of Electronic Publication: 2019 Jul 26. - Publication Year :
- 2019
-
Abstract
- Chemotherapy-induced peripheral neuropathy (PN) is a disorder damaging the peripheral nervous system (PNS) and represents one of the most common side effects of chemotherapy, negatively impacting the quality of life of patients to the extent of withdrawing life-saving chemotherapy dose or duration. Unfortunately, the pathophysiological effects of PN are poorly understood, in part due to the lack of availability of large numbers of human sensory neurons (SNs) for study. Previous reports have demonstrated that human SNs can be directly converted from primitive CD34 <superscript>+</superscript> hematopoietic cells, but was limited to a small-scale product of SNs and derived exclusively from less abundant allogenic sources of cord or drug mobilized peripheral blood (PB). To address this shortcoming, we have developed and report detailed procedures toward the generation of human SN directly converted from conventionally drawn PB of adults that can be used in a high-content screening platform for discovery-based studies of chemotherapy agents on neuronal biology. In the absence of mobilization drugs, cryogenically preserved adult human PB could be induced to (i)SN via development through expandable neural precursor differentiation. iSNs could be transferable to high-throughput procedures suitable for high-content screening applicable to neuropathy for example, alterations in neurite morphology in response to chemotherapeutics. Our study provides the first reported platform using adult PB-derived iSNs to study peripheral nervous system-related neuropathies as well as target and drug screening potential for the ability to prevent, block, or repair chemotherapy-induced PN damage. Stem Cells Translational Medicine 2019;8:1180-1191.<br /> (© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)
- Subjects :
- Adult
Cell Differentiation
Cell Proliferation
Cells, Cultured
Drug Evaluation, Preclinical
Humans
Induced Pluripotent Stem Cells drug effects
Leukocytes, Mononuclear drug effects
Neural Stem Cells drug effects
Peripheral Nervous System Diseases chemically induced
Peripheral Nervous System Diseases pathology
Sensory Receptor Cells drug effects
Antineoplastic Agents pharmacology
Drug Discovery
Induced Pluripotent Stem Cells cytology
Leukocytes, Mononuclear cytology
Neural Stem Cells cytology
Peripheral Nervous System Diseases drug therapy
Sensory Receptor Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 2157-6580
- Volume :
- 8
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Stem cells translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31347791
- Full Text :
- https://doi.org/10.1002/sctm.19-0054