Bruce Bunnell, Ph.D.
Permanent URI for this communityhttps://hdl.handle.net/20.500.12503/31638
Chairman and Professor, Microbiology, Immunology & Genetics
Email: Bruce.Bunnell@unthsc.edu
Browse
Browsing Bruce Bunnell, Ph.D. by Subject "Animals"
Now showing 1 - 3 of 3
- Results Per Page
- Sort Options
Item Adipose-Derived Stem Cells from Obese Donors Polarize Macrophages and Microglia toward a Pro-Inflammatory Phenotype(MDPI, 2020-12-25) Harrison, Mark A. A.; Wise, Rachel M.; Benjamin, Brooke P.; Hochreiner, Emily M.; Mohiuddin, Omair A.; Bunnell, Bruce A.Macrophages and microglia represent the primary phagocytes and first line of defense in the peripheral and central immune systems. They activate and polarize into a spectrum of pro- and anti-inflammatory phenotypes in response to various stimuli. This activation is tightly regulated to balance the appropriate immune response with tissue repair and homeostasis. Disruption of this balance results in inflammatory disease states and tissue damage. Adipose stem cells (ASCs) have great therapeutic potential because of the potent immunomodulatory capabilities which induce the polarization of microglia and macrophages to the anti-inflammatory, M2, phenotype. In this study, we examined the effects of donor heterogeneity on ASC function. Specifically, we investigated the impact of donor obesity on ASC stemness and immunomodulatory abilities. Our findings revealed that ASCs from obese donors (ObASCs) exhibited reduced stem cell characteristics when compared to ASCs from lean donors (LnASCs). We also found that ObASCs promote a pro-inflammatory phenotype in murine macrophage and microglial cells, as indicated by the upregulated expression of pro-inflammatory genes, increased nitric oxide pathway activity, and impaired phagocytosis and migration. These findings highlight the importance of considering individual donor characteristics such as obesity when selecting donors and cells for use in ASC therapeutic applications and regenerative medicine.Item CRISPR based editing of SIV proviral DNA in ART treated non-human primates(Springer Nature, 2020-11-27) Mancuso, Pietro; Chen, Chen; Kaminski, Rafal; Gordon, Jennifer; Liao, Shuren; Robinson, Jake A.; Smith, Mandy D.; Liu, Hong; Sariyer, Ilker K.; Sariyer, Rahsan; Peterson, Tiffany A.; Donadoni, Martina; Williams, Jaclyn B.; Siddiqui, Summer; Bunnell, Bruce A.; Ling, Binhua; MacLean, Andrew G.; Burdo, Tricia H.; Khalili, KamelElimination of HIV DNA from infected individuals remains a challenge in medicine. Here, we demonstrate that intravenous inoculation of SIV-infected macaques, a well-accepted non-human primate model of HIV infection, with adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing construct designed for eliminating proviral SIV DNA, leads to broad distribution of editing molecules and precise cleavage and removal of fragments of the integrated proviral DNA from the genome of infected blood cells and tissues known to be viral reservoirs including lymph nodes, spleen, bone marrow, and brain among others. Accordingly, AAV9-CRISPR treatment results in a reduction in the percent of proviral DNA in blood and tissues. These proof-of-concept observations offer a promising step toward the elimination of HIV reservoirs in the clinic.Item Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis(MDPI, 2020-09-30) Wise, Rachel M.; Harrison, Mark A. A.; Sullivan, Brianne N.; Al-Ghadban, Sara; Aleman, Sarah J.; Vinluan, Amber T.; Monaco, Emily R.; Donato, Umberto M.; Pursell, India A.; Bunnell, Bruce A.Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4⁺ T helper (Th) and T regulatory (Treg) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less Th and Treg cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.