HUMBLE Cells Against Type II Diabetes and Obesity

Written by Panamdeep Thind and Edited by Olivia Cooper

Diabetes and obesity are health problems that many try to manage usually through lifestyle changes and medication, but technology is adding yet another tool to the arsenal. Joslin Diabetes Center’s Integrative Physiology and Metabolism section has developed a type of cell that decreases the risk of diabetes and obesity. Through CRISPR-Cas 9 technology to modify parts of the genome, researchers used a specific type of adipocyte, a cell that stores fats, to engineer HUMBLE (human brown-like) fat cells [1]. These engineered HUMBLE cells were based on heat-generating adipocytes also known as brown adipose tissue (BAT). Heat-generating adipocytes reduce one’s risk of type II diabetes and obesity and often are low in abundance within obese individuals [2]. Researchers determined a way to engineer white adipose tissue, or fat-storing adipocytes, to function as BAT cells by activating uncoupling protein 1 (UCP1), giving them the function of BAT cells to create HUMBLE cells. In order to successfully test the CRISPR-Cas9 engineered cells, the cells had to be transplanted within the body to see if they aided brown fat cells in treating ailments such as obesity and type II diabetes [2]. 

In order to test the viability of the technique, HUMBLE cells were introduced to different groups of mice. One group of mice were given a transplant of HUMBLE cells while another group was put on a severe diet. The effectiveness of the HUMBLE cells was measured based on the mice’s weight and sensitivity to insulin compared to the group with mice placed on a diet [1]. HUMBLE cells facilitated many factors that were inhibited through type II diabetes, such as the retention of glucose within the bloodstream [1]. One pattern among the mice that were transplanted with HUMBLE cells was that they reacted with the previously existing brown fat cells, and consequently released nitric oxide, a naturally produced chemical in the body that increases blood flow and strengthens the overall immune system, that lets the cells easily burn the fat instead of storing it [2]. The interaction of HUMBLE cells and brown fat-like cells releasing nitric oxide gas displays the successful outcome of HUMBLE cells within the body to digest fat. 

However, in order for the HUMBLE cells to work with the other cells in a body, they must be personalized to the individual cell structure, limiting their potential as a mainstream cure [1]. Furthermore, once the HUMBLE cells are generalized, they can then easily function within one’s body with a reduced risk of rejection. Due to the limitation of needed personalization for the cells to work in one’s body, scientists have developed a more generalized version of HUMBLE cells to use for biomaterials, which are synthetic materials used to construct artificial cell components. Biomaterials can extend the capabilities of the cells by directing the cells once they have entered the body, eliminating the necessity to tailor cells to each individual [3]. Another workaround to personalization is to use gene therapy within the body to activate UCP1, without engineering HUMBLE cells. This method of activating repressed genes works in one of two ways: with the use of biological vectors, which aid in directing the gene to be activated, or physico-chemical methods, like DNA replication manipulation [4]. With further research, both of these alternative methods may serve as promising methods to personalize HUMBLE cells for use in treating conditions such as obesity and type II diabetes on a larger and more practical scale.

References: 

1. Wang, C., Lundh, M., Fu, A., Kriszt, R.,  Huang, T.L.,  Lynes, M.D., Leiria, L.O., Shamsi, F., Darcy, J., Greenwood, B.P.,  Narain, N.R., Tolstikov, V., Smith, K.L., Emanuelli, B., Chang, Y., Hagen, S., Danial, N.N., Kiebish, M.A., Tseng, Y. (2020) CRISPR-engineered human brown-like adipocytes prevent diet-induced obesity and ameliorate metabolic syndrome in mice. Science Translational Medicine, 12:558.
2. Wang, C., Lundh, M., Fu A., Kriszt R., Tian L.H. (2020). CRISPR-Engineered Human Brown-like Adipocytes Prevent Diet-Induced Obesity and Ameliorate Metabolic Syndrome in Mice. Science Translational Medicine, American Association for the Advancement of Science, 12:1-14.
3. Facklam, A.L., Volpatti L.R., Anderson D.G. (2019). Biomaterials for Personalized Cell Therapy. Advanced Materials, 32:1902005.
4. Verma, I.M., Naldini, L., Kafri T., Miyoshi H., Takahashi M. (1997). Gene Therapy: Promises, Problems and Prospects. SpringerLink, 389:239–242.