WISP-1 as the Bone Formation promoting factor in Stem Cells
Findings from this study suggest the ability to be able to "program" stem cells into forming bone tissue.
In recent years, stem cells -- unspecialized cells that are able to form many different cell types -- have been an area of focus for use in treatments to create or replace damaged tissue. One such investigation involved stem cells derived from adipose tissue, of which there are two types. Perivascular stromal cells (PSC) were found to form bone tissue much more efficiently that the stromal vascular fraction (SVF) of adipose tissue, but the reason why remained unclear.
Results from an experiment conducted by Dr. James and researchers at the Johns Hopkins School of Medicine suggest that the protein WNT1-inducible-signaling pathway protein 1 (WISP-1) may be the reason why.
WISP-1, a protein belonging to the connective tissue growth factor family, has previously been associated with cell development and survival. The researchers point to previous studies that have recognized WISP-1 as a factor that increases Wnt and BMP signaling and determines whether or not PSCs – which have the ability to become adipose tissue or bone – form bone cells.
In his current study, Dr. James investigated how manipulating WISP-1 expression in PSCs would influence bone development. To do this, PSCs were genetically modified such that they would stop producing WISP-1. In these cells, they observed decreased activity in genes involved in bone growth. When WISP-1 expression was increased however, the activity of these genes increased significantly compared to stem cells with normal levels of WISP-1.
Next, researchers investigated how WISP-1 could act to improve bone healing after a spinal fusion surgery. A procedure which Dr. James explains requires an abundance of bone cells:
“If we could direct bone cell creation at the site of the fusion, we could help patients recover more quickly and reduce the risk of complications.”
Their approach involved the injection of PSCs with active WISP-1 between the fused spinal bones of rats. Four weeks following the procedure, bone tissue began forming in the vertebrae and the spinal bones were starting to be fused. No fusion was observed at this time in rats that did not receive the WISP-1 treatment following surgery.
"We hope our findings will advance the development of cellular therapies to promote bone formation after surgeries like this one and for other skeletal injuries and diseases, such as broken bones and osteoporosis"
Future research projects for Dr. James include investigating whether inhibiting WISP-1 in PSCs can stimulate fat tissue production, which would be helpful for increased wound healing rates.