High Yield of Adult Oligodendrocyte Lineage Cells Obtained from Meningeal Biopsy

Abstract

Oligodendrocyte loss can lead to cognitive and motor deficits. Current remyelinating therapeutic strategies imply either modulation of endogenous oligodendrocyte precursors or transplantation of in vitro expanded oligodendrocytes. Cell therapy, however, still lacks identification of an adequate source of oligodendrocyte present in adulthood and able to efficiently produce transplantable cells. Recently, a neural stem cell-like population has been identified in meninges. We developed a protocol to obtain high yield of oligodendrocyte lineage cells from one single biopsy of adult rat meningeal tissue. From 1 cm2 of adult rat spinal cord meninges, we efficiently expanded a homogenous culture of 10 millions of meningeal-derived oligodendrocyte lineage cells in a short period of time (approximately 4 weeks). Meningeal-derived oligodendrocyte lineage cells show typical mature oligodendrocyte morphology and express specific oligodendrocyte markers, such as galactosylceramidase and myelin basic protein. Moreover, when transplanted in a chemically demyelinated spinal cord model, meningeal-derived oligodendrocyte lineage cells display in vivo-remyelinating potential. This oligodendrocyte lineage cell population derives from an accessible and adult source, being therefore a promising candidate for autologous cell therapy of demyelinating diseases. In addition, the described method to differentiate meningeal-derived neural stem cells into oligodendrocyte lineage cells may represent a valid in vitro model to dissect oligodendrocyte differentiation and to screen for drugs capable to promote oligodendrocyte regeneration.

Detecting Neurodevelopmental Toxicity of Domoic Acid and Ochratoxin A Using Rat Fetal Neural Stem Cells

“…Hence, we used the rNSC monolayer-based system to investigate the effects in the presence and absence of DA and OTA on the cytotoxicity and degree of differentiation of rNSC into oligodendrocytes, astrocytes, and neurons. For the astrocytes and neurons, the differentiation media has been described by others; for differentiation into oligodendrocytes, differentiation medium was supplemented with neurogenic 2% B27 (components are listed in the Materials and Methods section), which is known to enhance maximum in vitro survival, improved maturation, and functionality of pluripotent stem cell (PSC)-derived neurons [32,33,34].…”

Meninges: A Widespread Niche of Neural Progenitors for the Brain

“…8). Importantly, the in vitro cultured meningeal NSCs can undergo neuronal differentiation following transplantation in the hippocampus (Bifari and others 2009) and express myelinating potential following transplantation in the spinal cord (Dolci and others 2017). The feasibility of obtaining NSC-like culture from the meninges is remarkable for the following reasons: • • Meningeal NSCs can potentially be used in autologous graft setting.…”

“…In addition, in meninges have been observed boundary cap cells, which display stem cell properties and participate in the formation of the boundary between the CNS and the peripheral nervous system ( Zujovic and others 2011 ), and telocytes, which are interstitial cells characterized by extremely long cell processes, telopodes, establishing contacts with blood capillaries, nerve fibers, and stem cells ( Popescu and others 2012 ). Furthermore, a surprising discovery was made in the past few years when several groups described the presence of neural precursors in meninges ( Belmadani and others 2015 ; Bifari and others 2009 ; Bifari and others 2015 ; Bifari and others 2017 ; Dang and others 2019 ; Decimo and others 2011 ; Dolci and others 2017 ; Kumar and others 2014 ; Nakagomi and others 2011 ; Nakagomi and others 2012 ; Ninomiya and others 2013 ). The distribution and the relative abundance of all the different cell types may vary according to the specific meningeal locations, developmental times or physiological versus pathological conditions ( Fig.…”

Metabolism of Stem and Progenitor Cells: Proper Methods to Answer Specific Questions

“…NSCs have multipotent differentiation potentials and differentiated cells greatly modify their cellular morphology (Decimo et al, 2012a,b). Differentiating oligodendrocytes progressively expand cellular branching, reaching a mean of about 20 branching/cell (Butt et al, 1994; Dolci et al, 2017). All these differentiation stages are accompanied by specific changes in cellular metabolism (Lange et al, 2016; Knobloch and Jessberger, 2017; Beyer et al, 2018).…”