Novel method allows long-term culturing of adult stem cells
Researchers at Massachusetts General Hospital (MA, USA) have developed a novel procedure for generating and expanding adult stem cell lines.
Researchers led by Jayaraj Rajagopal at Massachusetts General Hospital (MA, USA) have developed a novel method for culturing adult stem cells from routinely-taken tissue samples. The study describes a simplified and minimally invasive technique for the enhanced generation and expansion of airway stem cell lines.
This research focused on a cellular signaling pathway that is responsible for regulating cell growth and differentiation. Activated by proteins such as TGF-beta and BMP, and transmitted to the nucleus by SMAD proteins, these SMAD signaling pathways were demonstrated to be active in differentiated cells but not in adult stem cells.
When SMAD signaling was inhibited in mouse airway stem cells, differentiation was prevented. Likewise, the inhibition of both TGF-beta and BMP pathways allowed the expansion of many generations of airway stem cells. Importantly, using the same technique, the investigators next generated and maintained human airway stem cells from samples taken from routine bronchoscopy, as well as from cough-induced sputum.
“If we could find ways to induce cough samples containing larger numbers of stem cells, our technique would represent the least invasive way to obtain any stem cell from any organ, and if we could improve the procedure to yield stem cell cultures from 100 percent of sputum samples, we could acquire samples to study lung disease in the laboratory with less invasiveness than a blood draw,” stated Rajagopal.
It is believed that this enhanced ability to maintain and expand adult stem cell populations will improve disease modeling, personalized therapeutic drug screening and the ability to create human knock-out/knock-in cellular models through CRISPR-Cas9 gene-editing technology. Additionally, by eliminating the necessity for the mouse cells that are traditionally utilized to support human airway stem cells in culture, this technology removes the risk of introducing contaminants and could enhance the safety of stem cell-based therapies.
While this technology maintains the function of adult stem cells through many generations, the next goal will be to eliminate the eventual loss of function. “We have lots of ideas and collaborations in place to try and sort out ways to make these cells nearly perfect,” concluded Rajagopal.
— Written by Adam Price-Evans
Sources: Mou H, Vinarsky V, Tata PR et al. Dual SMAD signaling inhibition enables long-term expansion of diverse epithelial basal cells. Cell Stem Cell doi:10.1016/j.stem.2016.05.012 (2016) (In Press Corrected Proof); www.massgeneral.org/News/pressrelease.aspx?id=1952