Top 5 Cytocentric Publications of 2017
With the first approvals of CAR-T, 2017 was a big year for cell-based research and therapies. Some scientific publications stood out from the rest as far as Cytocentric™ advancement. These publications not only encompass cutting-edge cell therapies, but also discoveries that were only made because researchers provided physiologically-relevant conditions for their cells in vitro.
#5 Sex differences in the mitochondrial bioenergetics of astrocytes but not microglia at a physiologically relevant brain oxygen tension. Jaber, S.M. and Bordt, E.A, et al. Neurochem Int, (2017).
This group found that in physioxia, astrocytes display different metabolic capacity depending upon whether they were isolated from male or female rats. It is work like this that will help reveal fundamental biological differences that have been hidden by supraphysioxic room air cell culture conditions. See our interview with the young co-first authors, Sausan Jaber and Evan Bordt here. Also, Dr. Bordt has a recent review out on exactly how critical physiologically relevant oxygen is for neuroscience here.
#4 Culturing CTLs under Hypoxic Conditions Enhances Their Cytolysis and Improves Their Anti-tumor Function, Y. Gropper, et al. Cell reports, 20 (2017) 2547-2555.
This remarkable paper showed that while cytolytic T cells proliferate more slowly at 1% O2 than at 20% oxygen, they produce larger amounts of granzyme B and kill tumors better in mice. It is Cytocentric work like this that will help bridge the distance between our understanding of T cell function in vitro and in vivo. It also contributes to a growing understanding of the importance of oxygen and metabolism in immune cell function.
#3 An oxygen sensitive self-decision making engineered CAR T-cell, A. Juillerat, et al. Scientific reports, 7 (2017) 39833.
Along with #4 above, the authors of this paper have made a significant contribution to the nascent field of Immunometabolism. In this case, they added a new tool, engineered a CAR-T cell that not only has a multi-chain T cell receptor, but also activates in hypoxic conditions in vitro. So in low-oxygen environments, like highly oxygen-competitive solid tumors, these cells kill more cancer cells. This is taking a vulnerability of T cells in solid tissues and turning it to their advantage. We are looking forward to the future publications of this group as they apply their new CAR-T tool.
#2 Using CRISPR-Cas9 to Generate Gene-Corrected Autologous iPSCs for the Treatment of Inherited Retinal Degeneration. E.R. Burnight, et al. Molecular therapy 25 (2017) 1999-2013.
The human immune system can limit the ability to replace malfunctioning cells with new, genetically repaired cells. This group not only used induced pluripotent stem cells (iPSC) from patients grown in a cGMP Cytocentric facility to generate new retinal cells, but also replace the defective gene in those cells using the highly selective CRISPR-Cas9 technology. Repairing the patients’ own cells to cure blindness, this approach can avoid the perils of immune rejection. This remarkable group from University of Iowa also published this year in current protocols on deriving cGMP-compliant patient-derived iPSC from skin biopsies and published on using these iPSC for evaluating gene-specific pathologies related to blindness here. Keep an eye out for our upcoming interview with senior author Dr. Budd Tucker, where we talk about their program and how being Patientcentric means being Cytocentric.
# 1 Islet Transplantation Provides Superior Glycemic Control With Less Hypoglycemia Compared With Continuous Subcutaneous Insulin Infusion or Multiple Daily Insulin Injections. D.J. Holmes-Walker, et al. Transplantation, 101 (2017) 1268-1275.
This report on a small clinical trial showed the potential benefit of using islets processed in a Cytocentric facility. They report on a study of 10 patients that switched from using multiple daily injections to continuous subcutaneous insulin infusion and then to transplanted human pancreatic islets. When they were transplanted with islets, the patients experienced the biggest benefits, decreasing hypoglycemic episodes and providing steadier blood glucose levels. The potential improvement of global human health and the reduction in overall heathcare costs through finding an effective treatment for diabetes is enormous.
We are standing on the edge of a new era in cell-based therapies. This is the fulfillment of the dream of regenerative medicine and we very much look forward to seeing more patients benefit from the Cytocentric approach to cell incubation and handling.
About the Author
Alicia D Henn, PhD, MBA
Alicia Henn has been the Chief Scientific Officer of BioSpherix, Ltd for two years. Previously, she was a researcher at the Center for Biodefense Immune Modeling in Rochester, NY. Alicia obtained her PhD in molecular pharmacology and cancer therapeutics from Roswell Park Cancer Institute in Buffalo, NY and her MBA from the Simon School at University of Rochester in Rochester, NY.