Skeletal Tissue Stem Cell Working Group
This Working Group explores novel activities of stem cells which will be exploited to develop effective, safe, and durable therapies for muscle, bone, cartilage and skin diseases. The basic scientists and physician scientists in this group collaborate to efficiently address important translational problems. Several researchers in the group exploit tissue bioengineering with stem cells to advance translation of the basic research advances into clinical treatments to repair skeletal tissues damaged in injury, disease and ageing.
The Nurminskaya group examines novel approaches to control and enhance formation of the cartilage implants with clinically relevant mesenchymal stem cells. These studies employ novel protein coatings for electrospun nanofibrous scaffolds combined with use of specific small molecule regulators to promote cartilage formation. In addition, the group is interested in understanding the molecular mechanisms of the reduced regenerative capacity of articular cartilage in osteoarthritis. These results will contribute to the development of allogeneic “off-the-shelf” stem cell therapies to improve cartilage repair with autologous and allogeneic stem cells.
Shanmugasundaram S, Logan-Mauney S, Burgos K, Nurminskaya M. Tissue transglutaminase regulates chondrogenesis in mesenchymal stem cells on collagen type XI matrices.Amino Acids. 2012 Feb;42(2-3):1045-53.
Lin X, Shanmugasundaram S, Liu Y, Derrien A, Nurminskaya M, Zamora PO. B2A peptide induces chondrogenic differentiation in vitro and enhances cartilage repair in rats. J Orthop Res. 2012 Aug;30(8):1221-8.
Bruce Yu, Ph.D.
Dr. Yu develops artificial extracellular matrices (ECMs) for stem cell culture in both 2D and 3D. His current interest is to engineer ECMs with unnatural chirality to direct stem cell biology. Natural ECMs are made of homochiral L-peptides and D-saccharides. The artificial ECMs made by Dr. Yu’s group have a range of chirality compositions, including homochiral, heterochiral and racemic. The goal is to use chirality as a tool to guide stem cell proliferation and differentiation.
Hyland, L., Twomey, J., Vogel, S., Hsieh, A., Yu, Y. B. (2013) Enhancing biocompatibility of D oligopeptide hydrogels by negative charges. Biomacromolecules, 14, 406-412.
The Lu-Chang group is interested in enhancing the efficiency of generation of induced pluripotent stem cells (iPSCs). We aim to reactivate the key pluripotency regulator, OCT4, through altering its epigenetic state. Thymine DNA glycosylase (TDG) is an essential multifunctional enzyme involved in DNA repair, DNA demethylation, and transcription regulation. It has been shown that TDG can activate OCT4. We have shown that SIRT1 (a member of class III NAD+-dependent histone/protein deacetylases) can activate OCT4 gene expression. We have demonstrated that TDG glycosylase activity is enhanced by interaction with SIRT1. Thus, we hypothesize that the expressing SIRT1 and TDG or employing their modulators will affect reprogramming. By using DNA repair enzymes and epigenetic regulators, the derived iPSCs should be high proliferative, tolerant to oxidative stress, and highly similar to ES cells.
Drs. Stains and Koh collaborate to examine the use of mesenchymal stem cells to overcome the inflammatory and catabolic environment of the joint during osteoarthritis. Further, we are looking to enhance the protective ability of these mesenchymal stem cells by taking advantage of their ability to establish direct cell-to-cell communications with host tissues. The ultimate goal is to use and to improve the efficacy of mesenchymal stem cells to slow the progression of degenerative diseases, like osteoarthritis.
Dr. Zhang’s group has been studying several skeletal stem cells over the past decade, including mesenchymal stem cells (MSCs) and tendon stem cells. The major goal of his research is develop better strategies for isolation, characterization and use of these different stem cells in tissue repair and regeneration. Previously, they identified a unique MSC marker and demonstrated its utility in the isolation of MSCs from the bone marrow by cell sorting. They also identified tendon stem cells and established proof-of-principle for their use in tendon repair. Currently, his group is studying the role of embryonic origin in MSC proliferation, differentiation and signaling. The information generated will help design optimal stem cell-based therapies for human patients.
The Zalzman group studies the fundamental mechanisms controlling cellular immortality and telomere repair. For our study, we use adult mesenchymal stem cells (MSCs) as an in vitro model for aging and telomere damage. Our lab develops novel protocols to promote transient telomere rejuvenation in order to enhance the replicative life span and expansion potential of adult stem cells. This research will allow the large scale expansion of MSCs required for future therapies of numerous diseases that are currently candidates for MSC treatment.
Zalzman M, Falco G, Sharova LV, Nishiyama A, Thomas M, Lee SL, Stagg CA, Hoang HG, Yang HT, Indig FE, Wersto RP, Ko MS. Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature. 2010. 464(7290):858-63.
Dr. Hsieh’s group employs cellular engineering approaches to elucidate cell-matrix interactions, through a combination of biological manipulation and device design. In particular, his research team has recently been focused on the formation of the pericellular matrix during chondrogenic differentiation, cellular remodeling of collagen matrices, and stem cell behavior and differentiation in microgravity. Their work seeks to develop novel strategies for enhancing stem cell-based therapeutics for degenerative musculoskeletal conditions.