Novel stem cell culture leads to osteoporosis prevention in diabetics
New insights reveal the cellular relationship between osteoporosis and diabetes, and provide an avenue to potential medical therapies.
It has been long known that both type I and II diabetics have an increased risk of osteoporosis, a disorder identified by having a low bone mass and deterioration of the bone. It is also known that diabetes stymies the regulation of the bone marrow environment, composed of adipocytes and osteoblasts; this deregulation then leads to the development of osteoporosis (Rinker, Hammoudi, Kemp, Lu, & Temenoff, 2014).
The researchers in the Temenoff lab at Georgia Tech have taken it upon themselves to examine this relationship between diabetes, osteoporosis, and the cellular bone marrow environment. By investigating the interactions of three types of cells in the bone marrow-mesenchymal stem cells (MSCs), adipocytes, and osteoblasts-in diabetic conditions, the Temenoff lab group hopes to gain insights into potential discrepancies between a diabetic bone marrow environment and a healthy bone marrow environment. The knowledge gained would aid in understanding the causes of osteoporosis in diabetics.
Spearheaded by graduated students Torri Rinker and Taymour Hammoudi under the direction of Professors Johnna Temenoff and Hang Lu, a novel method of 3D cell culture was developed that uses a tri-culture model of MSCs, adipocytes, and osteoblasts, as well as mono-cultures and co-cultures (osteoblasts with MSCS and adipocytes with MSCS) of these same cell types. All cell cultures were tested in both normal and high glucose environments; the latter to recapitulate a diabetic bone marrow environment. Cellular activity in this experiment was analyzed using gene expression, viability, histological markers, and MSC colony forming potential over seven days in culture.
The findings showed several significant relationships between cell types in normal and high glucose environments. The first was the presence of osteoblasts influences adipocyte behavior. However, the exact osteoblast behaviors that influence adipocytes are still unknown. The next result was that MSC clonogenicity and viability decreased in the presence of osteoblasts and in high glucose conditions. Despite the poor viability of MSCs in the presence of osteoblasts, the osteoblasts themselves had constant viability throughout the culture. This leads to the thought that MSCs act in a way to support osteoblasts in differing glucose levels at their own demise.
The interactions observed between MSCs and adipocytes differed greatly from the interactions between MSCs and osteoblasts. In the co-culture and tri-culture experiments of MSCs and adipocytes, there was maintenance of viability and clonogenicity in MSCs. In fact, "adipocytes may 'buffer' MSCs form the reduction of clonogenicity and viability induced by hyperglycemic conditions" (Rinker et al., 2014). This result indicates that in high glucose conditions, it is possible that a high number of adipocytes may deploy mechanisms to maintain the function of MSCs and hinder the development of osteoporosis.
The research being in the Temenoff lab has greatly contributed to the stem cell and osteoporosis fields. First and foremost, cutting-edge technology was developed to simultaneously study the cellular response to a disease condition as well as intercellular interactions. The results supported that the study of pathological environments is best performed in a multi-cell system. The findings also suggest that adipocytes play a strong role in the maintenance of MSC and osteoblast viability and clonogenicity. This information can then be used in future studies to develop therapies for osteoporosis onset in diabetics. Not only are the biological insights of Rinker and Hammoudi's work impactful, but also they provide the scientific community with novel cell culture technologies that can be employed to study nearly any in vitro disease model.
- Rinker, T. E., Hammoudi, T. M., Kemp, M. L., Lu, H., & Temenoff, J. S. (2014). Interactions between mesenchymal stem cells, adipocytes, and osteoblasts in a 3D tri-culture model of hyperglycemic conditions in the bone marrow microenvironment. Integr Biol (Camb), 6(3), 324-337. doi: 10.1039/c3ib40194d