To cell biologists, adipose tissue is more than just fat.
When referred to as “fat”, it is the only tissue in the body that can noticeably change its mass after adult size is reached. The dysregulation of adipose tissue has been linked to a variety of pathologies, including obesity, insulin resistance, and atherosclerosis (Thompson et al., Journal of Lipid Research, 2012; 53(12);2797). For instance, being overweight increases one’s likelihood of developing the common type of diabetes, Type 2 diabetes. With obesity on the rise, diabetes and related diseases are becoming health issues of increasing concern.
As a consequence of this, adipose tissue has been used as a source of cells in cell therapy.
How? Adipose tissue contains numerous immune cells and is a good source of stem cells. Specifically, adipose tissue contains many stromal stem cells. They can be found in both subcutaneous and omental fat. Because it is relatively easy to obtain in large quantities, it is considered a convenient source of stromal stem cells. These are commonly referred to as “adipose-tissue derived stem cells.” Such stem cells are obtained generally after liposuction by harvesting what is called the lipoaspirate. Cells are isolated from the lipoaspirate following washing and lysing red cells. This is where digestive enzymes come into play. The resultant floating adipose tissue is digested with enzymes such as collagenase before being centrifuged. The recovery of ADSCs can be improved by manipulating the centrifugation speed (Gimble et al. Circulation Research; 2007, 100). The pellet that results from centrifugation is referred to the SVF, and contains, apart from stromal cells, also endothelial cells, smooth muscle cells, pericytes, fibroblasts, leukocytes and hematopoietic stem cells. Because adipose-derived stem cells are adherent to plastic cultureware, they are self-selected out of the SVF during subsequent tissue culture passages.
Cells with a CD45-, CD31-, CD34+ and CD105+ surface phenotype can be freshly isolated from this by magnetic bead coupling. These cells are known to form CFU-F, proliferate and can be differentiated towards several lineages including osteogenic, chrondrogenic, adipogenic and neurogenic. As such, they are are considered pluripotent.
Expression profiles of isolated ADSC can be obtained by performing, for instance, a whole human genome oligo microarray analysis with a special emphasis on ECM and adhesion molecules.
In cell therapy, these stem cells, when delivered into an injured or diseased tissue, are thought to secrete growth factors to stimulate recovery. They also stimulate the recruitment of endogenous stem cells to the site and promote their differentiation.
An important, growing application of adipose-derived stem cells exploits their ability to differentiate into the cardiomyocyte lineage. This addresses 38% of all Americans that die each year, and is a $500+ bn market.
Traditional methods to isolate stem cells from adipose tissue include digestions with commercial enzyme formulations such as LiberaseTM and DispaseTM or, as mentioned above, enzymes such as collagenase derived from Clostridium. However, issues such as source and efficacy are a concern for some of these enzymes.
Because tissue dissociation is a key proteolytic activity in cell biology, the importance of optimal formulations of dissociation enzymes is a key concern.
To that end, Akron has developed a brand new, industry-first enzyme family named MatrixymeTM. This is a complete family of novel engineered enzymes capable of catalyzing the degradation of virtually all extracellular matrix (ECM) components, with the goal of liberating viable stem cells.
We are very pleased to announce the launch of the first formulation in the line, MatrixymeTM I. Unlike formulations currently present on the market, MatrixymeTM I isn’t derived from cellular toxins and is thus completely biologically safe.
MatrixymeTM represents the result of years of research in collaboration with the Torrey Pines Institute for Molecular Studies, for which Akron was recently awarded an SBIR grant.
MatrixymeTM I will be commercially available in the coming weeks. Contact us to be the first one to try some and keep checking back as we continue to add to the MatrixymeTM family.