This can be explained in part by their intrinsically low telomerase activity, eradicating the risk of tumorigenesis through unbridled cell proliferation.
[24] Similarly, epiblast stem cells cultured under certain conditions also do not form teratomas in testes, even though they show pluripotency in vitro.
Without need of cytokine induction or artificial gene manipulation, Muse cells are capable of repairing tissues when directly infused into the blood stream.
They are preexisting pluripotent stem cells that normally reside in the bone marrow, peripheral blood and connective tissue of every organ including the umbilical cord.
[31] Muse cells are able to self-renew, maintaining their proliferative activity, pluripotency marker expression and a normal karyotype.
They can also be isolated from skin fibroblasts obtained via skin biopsy, adipose tissue obtained by liposuction and from the umbilical cord; a safe and non-invasive procedure often used for cosmetic surgery interventions[9] Easy accessibility of Muse cells allows them to be auto- or allo-transplanted in regenerative clinical applications.
Application of a cytokine induction system comprising Wnt3a, SCF, ET-3, basic fibroblast growth factor, linoleic acid, cholera toxin, L-ascorbic acid, 12-O-tetradecanoylphorbol 13-acetate, insulin, transferrin, selenium, and dexamethasone to both human dermal fibroblast-derived Muse and non-Muse cells induces only the Muse cells into L-DOPA–reactive functional melanocytes capable of melanin production in a 3D cultured skin model.
In addition, Muse cluster expanded cells differentiate into osteoblasts positive for osteocalcin using dexamethasone, ascorbic acid, and β-glycerophosphate.
Infarct size was reduced by ≈52%, and the ejection fraction was increased by ≈38% compared with vehicle injection at 2 months, ≈2.5 and ≈2.1 times higher, respectively, than that induced by mesenchymal stem cells.
[20] The similar therapeutic effect was observed in swine acute myocardial infarction model that received human-Muse cell intravenous injection.
In a rat stroke model induced by ischemic-reperfusion of middle cerebral artery occlusion (MCAO), 3 x 104 human dermal-Muse cells topically injected into three sites in the infarct area (each site received 1 x 104 Muse cells) delivered statistically significant functional recovery compared to vehicle and non-Muse fibroblast cell-injected groups after ~2.5 months.
The functional recovery was supported by the incorporation of human Muse cells into rat pyramidal and sensory tracts with normalized hind limb somatosensory evoked potentials.
[37][55] In the mouse lacunar stroke model, human Muse cells-derived neuronal cells integrated into the pyramidal tract, leading to statistically meaningful functional recovery.
[56] Intravenously injected human bone marrow-derived Muse cells are able to repair an immunodeficient mouse (SCID) model of CCL4-induced liver cirrhosis.
[51][52] In the pig hepatectomy model, allogenic Muse cell intravenous injection delivered liver tissue repair and functional recovery.
[57] Human bone marrow-derived Muse cells injected intravenously repair SCID and BALB/c mouse models of focal segmental glomerulosclerosis without added immunosuppression.
[38] Human adipose tissue-derived Muse-rich cells significantly accelerate wound healing in skin ulcers of a mouse type 1 diabetes model.
[58] Therapeutic efficacy of intravenous injection of human bone marrow-Muse cells into a SCID mouse aortic aneurysm model was evaluated.
Notably, all the mice in the Muse group showed the linear deposition of human type VII COL (hCOL7) at the injury site of the mouse skin whereMuse-derived cells were intensively integrated.
Magnetic resonance spectroscopy and positron emission tomography demonstrated that Muse cells dampened excitotoxic brain glutamatergic metabolites and suppressed microglial activation.
Intravenously transplanted Muse cells afforded functional benefits in experimental HIE possibly via regulation of glutamate metabolism and reduction of microglial activation.
[60] In G93A-transgenic ALS mice, intravenous injection of 5.0 × 10^4 Muse cells revealed successful homing to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression.
These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death.
[61] Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis, hemolytic uremic syndrome, and acute encephalopathies that may lead to sudden death or severe neurologic sequelae.
Thus, intravenous administration of Muse cells could be a candidate therapeutic approach for preventing fatal encephalopathy after STEC infection.
These activated Muse spheroids enabled ready differentiation into corneal stromal cells (CSCs) expressing characteristic marker genes and proteins in vitro.
Intravenous injection of human umbilical cord-derived Muse cells increased the survival rate and the protection/repair of the gastrointestinal tract.