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Volume 02
Stem Cells 2019 & Pediatrics Congress 2019
November 06-07, 2019
Journal of Clinical Genetics and Genomics
November 06-07, 2019 | Tokyo, Japan
STEM CELLS AND REGENERATIVE MEDICINE
PEDIATRICS AND CHILD CARE
International Conference on
2
nd
World Congress on
&
J Clin Gen Genomics, Volume 02
Identification of a population of quiescent pluripotent stem cells within peripheral
nerves
Michael Heggeness
University of Kansas School of Medicine, USA
E
vidence from our laboratory has documented a large population of quiescent stem cells within peripheral nerves. In response
to nerve injury, or stimulation with the cytokines (eg BMP2), these cells proliferate and generate populations of pluripotent
stem cells, expressing Sox2, Klf4, Oct4 and c-Myc (verified by double stain immunohistochemistry and by real time PCR). These
4 markers are the transcription factors that confer embryonic pluripotency (Cell 126: 663, 2006). We call them nerve derived
pluripotent stem cells, or NEDAPS cells. The cells propagate well in restrictive media and are readily induced to form tissues
from all 3 germ layers. We hypothesize that pluripotent stem cells are indeed residing in peripheral nerves and they represent
the central feature in an important and previously unknown universal pathway for tissue repair. Nerves are nearly ubiquitous in
the body, from the cornea of the eye to every hair follicle. Thus, we believe that nerve injury and the consequent proliferation of
these stem cells, occurs following essentially any injury. The cell of origin for these pluripotent stem cells are the Schwann cells,
which have long been known to have remarkable plasticity, demonstrated by their behavior after a nerve transection. We believe
that we have uncovered a previously unknown universal pathway for healing.
We will show data documenting the induction and successful culture of these unique new pluripotent cells from three mammalian
species, mouse, rat and human and demonstrate their directed differentiation into osteoblasts, endothelial cells, primitive nerve
cells, definitive endoderm, brown fat and fibroblasts as demonstrated by morphology, immunohistochemical staining and by real
time polymerase chain reaction (RT-PCR) data to document cell specific gene expression.
Stem cell biology is a field that has recently seen an explosion of new work. stimulated by Dr Yamanaka’s remarkable discovery
that induced pluripotent stem cells (iPCs), or cells capable of differentiating into any cell type, could be created from fully
differentiated cells by forcing expression of the genes for only 4 transcription factors (listed above), most often by the use of
retrovirus vectors (Cell 126: 663,2006). Such iPCs are being widely studied as possible sources of cells for the treatment of
human disease. This work has been hampered by issues of malignant transformation of iPCs and by immune rejection of these
“non-self” cells. Previous claims to successful identification of cells with universal differentiation from non-gonadal adult tissue
have sadly resulted in some notable and well publicized scandals, involving fabricated data). These scandals have understandably
created a skeptical audience for us. Such pluripotent stem cells are thought not to exist in adult animals (SciON 311: 814 2006)
and until the recent discovery of these cells by our group, we believed the same.
We propose that this new knowledge will also explain the puzzling and vexing clinical problem of impaired wound healing
experienced by severely diabetic patients and victims of leprosy. We suggest that in the severe depletion or absence of Schwann
cells due to the severe neuropathies caused by these illnesses, essentially makes wound healing impossible. The other implication
of this discovery is that we may now have a straightforward opportunity to obtain individual specific “self-to-self” stem cell
treatments based on a minimally invasive biopsy of a nonessential peripheral neve of a specific patient in need, from which
NEDAPS cells could be easily propagated
ex vivo
. These NEDAPS cells could be differentiated into cells specifically needed by
the individual patient who provided the nerve tissue. We suspect that this scheme will bypass the risk of malignant transformation,
as well as immune rejection. This method has been successfully applied to a skin healing model, as well as fracture healing
models.
mheggeness@kumc.edu