Abstract
This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiation in vitro and after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grown in vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP) in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins.
Highlights
There is widespread enthusiasm for the prospect of some kind of cellular transplant therapy for repair of failing organs[1,2]
We show that adult, olfactory mucosa–derived, neural progenitor cells can be induced to differentiate into cells resembling cardiomyocytes when transplanted into the infarcted rat heart
Donor-derived cells were detected 35 days after transplantation. Most of these were integrated into the myocardium and expressed cardiac muscle contractile proteins
Summary
There is widespread enthusiasm for the prospect of some kind of cellular transplant therapy for repair of failing organs[1,2]. They have been demonstrated to be therapeutic in a rat model of Parkinson’s disease[4], where human olfactory neural stem cells were transplanted into rat brains Another pilot study demonstrated their ability to express chondrogenic phenotype in vitro and after transplant in a rat intervertebral disc model[5]. They are an attractive source of autologous stem cells because of the ease with which they can be obtained by simple biopsy of as little as 1 mm of tissue from a patient’s nose[3]. In a chick embryo transplant model, olfactory-derived cells (both adult human and adult mouse) were integrated into beating heart muscle and subsequently confirmed to express cardiac-specific protein[3]
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