NEW PATENT
Xie J, Jiang J, Nanofiber mats and production methods thereof. US provisional patent No. 62056899. 2014.
RECENT KEY PUBLICATIONS
Between April 2014 and April 2015, over 185 publications by Regenerative Medicine Faculty members have been published. These have been the work of 35 different faculty members.
Bele, A., S. Mirza, Y. Zhang, R. Mir, S. Lin, J. H. Kim, C. B. Gurumurthy, W. West, F. Qiu and H. Band (2015). "The cell cycle regulator Ecdysoneless cooperates with H-Ras to promote oncogenic transformation of human mammary epithelial cells." Cell Cycle (just-accepted): 00-00.
The mammalian ortholog of Drosophila ecdysoneless (Ecd) gene product regulates Rb-E2F interaction and is required for cell cycle progression. Ecd is overexpressed in breast cancer and its overexpression predicts shorter survival in patients with ErbB2-positive tumors. Dr. Band’s group demonstrated an important co-oncogenic role of Ecd in the progression of mammary oncogenesis through promoting cell survival.
Dey, P., S. Rachagani, A. P. Vaz, M. P. Ponnusamy and S. K. Batra (2014). "PD2/Paf1 depletion in pancreatic acinar cells promotes acinar-to-ductal metaplasia." Oncotarget 5(12): 4480.
Pancreatic differentiation 2 (PD2), a PAF (RNA Polymerase II Associated Factor) complex subunit, is overexpressed in pancreatic cancer cells and has demonstrated potential oncogenic property. Dr. Batra’s group showed loss of PD2/Paf1 expression during acinar transdifferentiation in pancreatic cancer initiation and PD2/Paf1 mediated regulation of lineage specific markers.
Hu, L., J. Liu, Z. Li, F. Ozturk, C. Gurumurthy, R. A. Romano, S. Sinha and A. Nawshad (2014). "TGFβ3 Regulates Periderm Removal through ΔNp63 in the Developing Palate." Journal of cellular physiology.
Dr. Nawshad and his associates performed biochemical analysis, gene activity and protein expression assays with palatal sections of TGFβ3 (-/-), ΔNp63 (-/-), and wild-type (WT) embryos, and primary MEE cells from WT palates to analyze the association between TGFβ3 and IRF6/ΔNp63. ΔNp63 is involved in multiple functions during skin development and in adult stem/progenitor cell regulation. Their results suggest that cleft palate occurs in TGFβ3 (-/-) because of inadequate periderm removal that impedes palatal seam formation, while cleft palate occurs in ΔNp63 (-/-) palates because of premature fusion.
Izuagie, I. A., C. J. Pelham and D. K. Agrawal (2015). "Synergistic effect of angiotensin II on vascular endothelial growth factor-A-mediated differentiation of bone marrow-derived mesenchymal stem cells into endothelial cells." Stem cell research & therapy 6(1): 4.
Increased levels of angiotensin II (Ang II) and activity of Ang II receptor type 1 (AT1R) elicit detrimental effects in cardiovascular disease. However, the role of Ang II receptor type 2 (AT2R) remains poorly defined. Mesenchymal stem cells (MSCs) replenish and repair endothelial cells in the cardiovascular system. Dr. Agrawal’s group reported the presence of functional AT2R receptor on porcine bone marrow-derived MSCs, where it positively regulates EC differentiation. These findings have significant implications toward therapeutic approaches based on activation of AT2R, which could be a means to stimulate regeneration of damaged endothelium and prevent vascular thrombosis.
Malhotra, G. K., X. Zhao, E. Edwards, J. L. Kopp, M. Naramura, M. Sander, H. Band and V. Band (2014). "The role of Sox9 in mouse mammary gland development and maintenance of mammary stem and luminal progenitor cells." BMC developmental biology 14(1): 47.
Identification and characterization of molecular controls that regulate mammary stem and progenitor cell homeostasis are critical to our understanding of normal mammary gland development and its pathology. Dr. Vimla Band’s group demonstrated that conditional knockout of Sox9 in the mouse mammary gland results in impaired postnatal development. These studies identify Sox9 as a key regulator of mammary gland development and stem/progenitor maintenance.
Parameswaran, S., X. Xia, G. Hegde and I. Ahmad (2014). "Hmga2 regulates self-renewal of retinal progenitors." Development 141(21): 4087-4097.
In vertebrate retina, histogenesis occurs over an extended period. To sustain the temporal generation of diverse cell types, retinal progenitor cells (RPCs) must self-renew. However, self-renewal and regulation of RPCs remain poorly understood. Here the authors demonstrate that cell-extrinsic factors coordinate with the epigenetic regulator high-mobility group AT-hook 2 (Hmga2) to regulate self-renewal of late retinal progenitor cells (RPCs). Their results provide a framework for integrating the diverse intercellular influences elicited by epigenetic regulators for self-renewal in a dynamic stem cell niche: the developing vertebrate retina.
Pysz, M. A., F. Hao, A. A. Hizli, M. A. Lum, W. M. Swetzig, A. R. Black and J. D. Black (2014). "Differential Regulation of Cyclin D1 Expression by Protein Kinase C α and ϵ Signaling in Intestinal Epithelial Cells." Journal of Biological Chemistry 289(32): 22268-22283.
Cellular accumulation of cyclin D1, a key regulator of cell proliferation and tumorigenesis, is subject to tight control. Dr. Black and her colleagues demonstrated that the recovery and hyperinduction of cyclin D1 reflect the combined effects of (a) loss of negative signals from PKCα due to agonist-induced PKCα down-regulation and (b) positive effects of PKCϵ. The differential effects of PKCα and PKCϵ on cyclin D1 accumulation are likely to contribute to the opposing tumor-suppressive and tumor-promoting activities of these PKC family members in the intestinal epithelium.
Romereim, S. M., N. H. Conoan, B. Chen and A. T. Dudley (2014). "A dynamic cell adhesion surface regulates tissue architecture in growth plate cartilage." Development 141(10): 2085-2095.
The architecture and morphogenetic properties of tissues are founded in the tissue-specific regulation of cell behaviors. In endochondral bones, the growth plate cartilage promotes bone elongation via regulated chondrocyte maturation within an ordered, three-dimensional cell array. Dr. Dudley and his associates present new mechanistic insights generated by application of a novel time-lapse confocal microscopy method along with immunofluorescence and electron microscopy. Their results support a model in which regulation of adhesive surface dynamics and cortical tension by extrinsic signaling modifies the thermodynamic landscape to promote organization of daughter cells in the context of the three-dimensional growth plate tissue.
Sargent, K. M., N. Lu, D. T. Clopton, W. E. Pohlmeier, V. M. Brauer, N. Ferrara, D. W. Silversides and A. S. Cupp (2015). "Loss of Vascular Endothelial Growth Factor A (VEGFA) Isoforms in Granulosa Cells Using pDmrt-1-Cre or Amhr2-Cre Reduces Fertility by Arresting Follicular Development and by Reducing Litter Size in Female Mice." PloS one 10(2).
VEGFA (Vascular Endothelial Growth Factor A) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. VEGFA has been implicated in follicle development. Dr. Cupp’s group determined the effects of granulosa- and germ cell-specific VEGFA loss on ovarian morphogenesis, function, and female fertility. They showed that the loss of all VEGFA isoforms in granulosa/germ cells (proangiogenic and antiangiogenic) causes subfertility by arresting follicular development, resulting in reduced ovulation rate and fewer pups per litter.
Sargus-Patino, C. N., E. C. Wright, S. A. Plautz, J. R. Miles, J. L. Vallet and A. K. Pannier (2014). "In vitro development of preimplantation porcine embryos using alginate hydrogels as a three-dimensional extracellular matrix." Reproduction, Fertility and Development 26(7): 943-953.
Between Days 10 and 12 of gestation, porcine embryos undergo a dramatic morphological change, known as elongation, with a corresponding increase in oestrogen production that triggers maternal recognition of pregnancy. Elongation deficiencies contribute to embryonic loss, but exact mechanisms of elongation are poorly understood due to the lack of an effective in vitro culture system. The objective Dr. Pannier’s study was to use alginate hydrogels as three-dimensional scaffolds that can mechanically support the in vitro development of preimplantation porcine embryos. Their Result illustrate that preimplantation pig embryos encapsulated in alginate hydrogels can undergo morphological changes with increased expression of steroidogenic transcripts and oestrogen production, consistent with in vivo-developed embryos.
Thakurta, S. G., G. Budhiraja and A. Subramanian (2015). "Growth factor and ultrasound-assisted bioreactor synergism for human mesenchymal stem cell chondrogenesis." Journal of Tissue Engineering 6.
Chondrogenesis is the process by which cartilage is developed. To achieve tissue-engineered cartilage using macroporous scaffolds, it is hypothesized that a combination of ultrasound at 5.0 MHz and transforming growth factor-β3 induces human mesenchymal stem cell differentiation to chondrocytes. Dr. Subramanian’s group results suggest that ultrasound at 5.0 MHz could be used to induce chondrogenic differentiation of mesenchymal stem cells for cartilage tissue engineering.
Lee, J. S., J. Y. Lim and J. Kim (2014). "Mechanical stretch induces angiotensinogen expression through PARP1 activation in kidney proximal tubular cells." In Vitro Cellular & Developmental Biology-Animal: 1-7.
Poly(ADP-ribose) polymerase 1 (PARP1) contributes to fibrosis in several disease models. Dr. Lim and colleagues report PARP1 activation after mechanical stretch of kidney proximal tubular cells enhances angiotensinogen expression via nuclear factor kappa B (NF-κB) activation. This data demonstrates that mechanical stretch-induced PARP1 activation contributes to angiotensinogen expression and NF-κB activation in kidney proximal tubular cells, resulting in the promotion of renal tubulointerstitial fibrosis and inflammation.
Xie, J., M. R. MacEwan, W. Liu, N. Jesuraj, X. Li, D. Hunter and Y. Xia (2014). "Nerve guidance conduits based on double-layered scaffolds of electrospun nanofibers for repairing the peripheral nervous system." ACS applied materials & interfaces 6(12): 9472-9480.
Compared to the nerve guidance conduits (NGCs) constructed from a single layer of aligned nanofibers, bilayer NGCs with random and aligned nanofibers in the outer and inner layers are more robust and tear-resistant during surgical procedures thanks to an isotropic mechanical property provided by the random nanofibers. However, it remains unclear whether the random nanofibers will interfere with the aligned nanofibers to alter the extension pattern of the neurites and impede regeneration. To answer this question, Dr. Xie’s group seeded dorsal root ganglia (DRG) on a double-layered scaffold, with aligned and random nanofibers on the top and bottom layers, respectively, and evaluated the outgrowth of neurites. They concluded that the bilayer NGCs hold great potential in facilitating motor axon regeneration and functional motor recovery.
Zhao, S. and L. Gu (2014). "Implementation and Validation of Aortic Remodeling in Hypertensive Rats." Journal of biomechanical engineering 136(9): 091007.
A computational framework was implemented and validated to better understand the hypertensive artery remodeling in hypertensive rats in both geometric dimensions and material properties. Dr. Gu’s results suggested that hypertension induced arterial remodeling is quite heterogeneous due to both nonlinear geometry and material adaptation process. Their computational model provided insights into the evolutions of morphology and material of the artery, which could complement the discrete experimental data for improving the clinical management of hypertension.