Abstract
BackgroundNeurological disorders are considered one of the greatest burdens to global public health and a leading cause of death. Stem cell therapies hold great promise for the cure of neurological disorders, as stem cells can serve as cell replacement, while also secreting factors to enhance endogenous tissue regeneration. Adult human multipotent stem cells (MSCs) reside on blood vessels, and therefore can be found in many tissues throughout the body, including palatine tonsils. Several studies have reported the capacity of MSCs to differentiate into, among other cell types, the neuronal lineage. However, unlike the case with embryonic stem cells, it is unclear whether MSCs can develop into mature neurons.MethodsHuman tonsillar MSCs (T-MSCs) were isolated from a small, 0.6-g sample, of tonsillar biopsies with high viability and yield as we recently reported. Then, these cells were differentiated by a rapid, multi-stage procedure, into committed, post-mitotic, neuron-like cells using defined conditions.ResultsHere we describe for the first time the derivation and differentiation of tonsillar biopsy-derived MSCs (T-MSCs), by a rapid, multi-step protocol, into post-mitotic, neuron-like cells using defined conditions without genetic manipulation. We characterized our T-MSC-derived neuronal cells and demonstrate their robust differentiation in vitro.ConclusionsOur procedure leads to a rapid neuronal lineage commitment and loss of stemness markers, as early as three days following neurogenic differentiation. Our studies identify biopsy-derived T-MSCs as a potential source for generating neuron-like cells which may have potential use for in vitro modeling of neurodegenerative diseases or cell replacement therapies.
Highlights
Neurological disorders are considered one of the greatest burdens to global public health and a leading cause of death
We developed a procedure to directly differentiate our tonsillar biopsy-derived stem cells (T-multipotent stem cells (MSCs)) and assessed their potential to generate neuron-like cells
We found that when equal number of cells were seeded in neurosphere conditions for 72 h, the tonsillar biopsy-derived MSCs (T-MSCs)-derived spheres were larger and more numerous compared to bone marrow derived MSCs (BM-MSCs)-derived neurospheres (Fig. 2A, B)
Summary
Neurological disorders are considered one of the greatest burdens to global public health and a leading cause of death. Adult human multipotent stem cells (MSCs) reside on blood vessels, and can be found in many tissues throughout the body, including palatine tonsils. Several studies have reported the capacity of MSCs to differentiate into, among other cell types, the neuronal lineage. Human multipotent stem cells (MSCs) [1], known as multipotent progenitor cells (MPCs) are stem cells residing on blood vessels, and can be found throughout the body [2,3,4]. Neuron-like cells have been generated from MSCs derived from bone marrow [20, 21], adipose tissue [22, 23], olfactory mucosa [24] and umbilical cord [25, 26]. Efficacy and safety of MSCs-based therapies were reported for neurodegenerative disorders such as Parkinson’s disease [33], Alzheimer’s disease [34, 35], ischemic stroke [36, 37], autism spectrum disorder [38] and amyotrophic lateral sclerosis [39, 40]
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