Canine epidermal neural crest stem cells: characterization and potential as therapy candidate for a large animal model of spinal cord injury.
The discovery of multipotent neural crest-derived stem cells, named epidermal neural crest stem cells (EPI-NCSC), that persist postnatally in an easy-to-access location-the bulge of hair follicles-opens a spectrum of novel opportunities for patient-specific therapies. We present a detailed characterization of canine EPI-NCSC (cEPI-NCSC) from multiple dog breeds and protocols for their isolation and ex vivo expansion. Furthermore, we provide novel tools for research in canines, which currently are still scarce. In analogy to human and mouse EPI-NCSC, the neural crest origin of cEPI-NCSC is shown by their expression of the neural crest stem cell molecular signature and other neural crest-characteristic genes. Similar to human EPI-NCSC, cEPI-NCSC also expressed pluripotency genes. We demonstrated that cEPI-NCSC can generate all major neural crest derivatives. In vitro clonal analyses established multipotency and self-renewal ability of cEPI-NCSC, establishing cEPI-NCSC as multipotent somatic stem cells. A critical analysis of the literature on canine spinal cord injury (SCI) showed the need for novel treatments and suggested that cEPI-NCSC represent viable candidates for cell-based therapies in dog SCI, particularly for chondrodystrophic dogs. This notion is supported by the close ontological relationship between neural crest stem cells and spinal cord stem cells. Thus, cEPI-NCSC promise to offer not only a potential treatment for canines but also an attractive and realistic large animal model for human SCI. Taken together, we provide the groundwork for the development of a novel cell-based therapy for a condition with extremely poor prognosis and no available effective treatment.
Stem Cell Program, Institute for Regenerative Cures Sacramento, California, USA; Department of Pathology, Microbiology and Immunology and Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA; Institute of Genetic Medicine, Centre for Life, Newcastle University, Newcastle upon Tyne, United Kingdom.
Barbara
B
Gericota
Joseph S
JS
Anderson
Gaela
G
Mitchell
Dori L
DL
Borjesson
Beverly K
BK
Sturges
Jan A
JA
Nolta
Maya
M
Sieber-Blum
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D015870:Gene Expression; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D015415:Biomarkers; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc; D055748:SOXB1 Transcription Factors
Adult stem cells; Canine epidermal neural crest stem cells; Dog model; EPI-NCSC; Hair follicle; Neural crest; Spinal cord injury; cEPI-NCSC