Isolation of Novel Multipotent Neural Crest-Derived Stem Cells from Adult Human Inferior Turbinate

Abstract

Adult human neural crest-derived stem cells (NCSCs) are of extraordinary high plasticity and promising candidates for the use in regenerative medicine. Here we describe for the first time a novel neural crest-derived stem cell population within the respiratory epithelium of human adult inferior turbinate. In contrast to superior and middle turbinates, high amounts of source material could be isolated from human inferior turbinates. Using minimally-invasive surgery methods isolation is efficient even in older patients. Within their endogenous niche, inferior turbinate stem cells (ITSCs) expressed high levels of nestin, p75(NTR), and S100. Immunoelectron microscopy using anti-p75 antibodies displayed that ITSCs are of glial origin and closely related to nonmyelinating Schwann cells. Cultivated ITSCs were positive for nestin and S100 and the neural crest markers Slug and SOX10. Whole genome microarray analysis showed pronounced differences to human ES cells in respect to pluripotency markers OCT4, SOX2, LIN28, and NANOG, whereas expression of WDR5, KLF4, and c-MYC was nearly similar. ITSCs were able to differentiate into cells with neuro-ectodermal and mesodermal phenotype. Additionally ITSCs are able to survive and perform neural crest typical chain migration in vivo when transplanted into chicken embryos. However ITSCs do not form teratomas in severe combined immunodeficient mice. Finally, we developed a separation strategy based on magnetic cell sorting of p75(NTR) positive ITSCs that formed larger neurospheres and proliferated faster than p75(NTR) negative ITSCs. Taken together our study describes a novel, readily accessible source of multipotent human NCSCs for potential cell-replacement therapy.

Olfactory ecto-mesenchymal stem cells possess immunoregulatory function and suppress autoimmune arthritis

“…12 Residing in the nasal cavity, OEMSCs are derived primarily from neural crest cells and possess a high proliferation rate, self-renewal capability, and multiple lineage differentiation capabilities. 13 Several studies have reported that OE-MSC transplantation can induce neurogenesis and restore hippocampal neuronal networks in mice. 14 However, it remains largely unknown whether OE-MSCs, which are similar to other types of MSCs, possess any immunoregulatory functions.…”

Human Turbinate-derived Mesenchymal Stem Cells Differentiated into Keratocyte Progenitor Cells

“…Various MSCs derived from cranial neural crest are involved in corneal stromal stem cells, dental pulp, periodontal ligament, skin and hair follicles, but these MSCs have the disadvantages that their detachment requires difficult surgery, and that they have restricted life span [31]. In contrast, surgery to obtain hTMSC is minimally invasive and causes minimal physical pain to the patient; it also provides the possibility of autologous therapy [23,37]. The present paper presents the possibility of hTMSCs to differentiate into keratocyte progenitor cells after 7D of KDM treatment.…”

Olfactory Mucosa Mesenchymal Stem Cells and Biomaterials: A New Combination to Regenerative Therapies after Peripheral Nerve Injury

“…Located in the olfactory region of the nasal cavity, OM-MSCs are primarily derived from neural crest cells, have a high proliferation rate, self-renewal ability and multiple lineage diferentiation capabilities [83]. These cells have already been isolated from human and mice [84], rat [85], rabbit [86] and dog [87], both with in vivo [84] and post-mortem protocols [86].…”