Translating G-CSF as an Adjunct Therapy to Stem Cell Transplantation for Stroke
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OPINION PAPER
Translating G-CSF as an Adjunct Therapy to Stem Cell Transplantation for Stroke Ike dela Peña 1 & Cesar V. Borlongan 2
Received: 18 August 2015 / Revised: 5 October 2015 / Accepted: 8 October 2015 # Springer Science+Business Media New York 2015
Abstract Among recently investigated stroke therapies, stem cell treatment holds great promise by virtue of their putative ability to replace lost cells, promote endogenous neurogenesis, and produce behavioral and functional improvement through their Bbystander effects.^ Translating stem cell in the clinic, however, presents a number of technical difficulties. A strategy suggested to enhance therapeutic utility of stem cells is combination therapy, i.e., co-transplantation of stem cells or adjunct treatment with pharmacological agents and substrates, which is assumed to produce more profound therapeutic benefits by circumventing limitations of individual treatments and facilitating complementary brain repair processes. We previously demonstrated enhanced functional effects of cotreatment with granulocyte-colony stimulating factor (GCSF) and human umbilical cord blood cell (hUCB) transplantation in animal models of traumatic brain injury (TBI). Here, we suggest that the aforementioned combination therapy may also produce synergistic effects in stroke. Accordingly, G-CSF treatment may reduce expression of pro-inflammatory cytokines and enhance neurogenesis rendering a receptive microenvironment for hUCB engraftment. Adjunct treatment of GCSF with hUCB may facilitate stemness maintenance and guide neural lineage commitment of hUCB cells. Moreover, regenerative mechanisms afforded by G-CSF-mobilized
* Ike dela Peña [email protected] 1
Department of Pharmaceutical and Administrative Sciences, Loma Linda University, Loma Linda, CA 92350, USA
2
Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA
endogenous stem cells, secretion of growth factors by hUCB grafts and G-CSF-recruited endothelial progenitor cells (EPCs), as well as the potential graft–host integration that may promote synaptic circuitry re-establishment could altogether produce more pronounced functional improvement in stroked rats subjected to a combination G-CSF treatment and hUCB transplantation. Nevertheless, differences in pathology and repair processes underlying TBI and stroke deserve consideration when testing the effects of combinatorial G-CSF and hUCB cell transplantation for stroke treatment. Further studies are also required to determine the safety and efficacy of this intervention in both preclinical and clinical stroke studies. Keywords G-CSF . hUCB cells . Stroke . Combination therapy
Introduction Stroke is a worldwide public health concern causing 5.5 million deaths and the annual loss of 49 million disabilityadjusted life years [1, 2]. Despite years of research, therapeutic options for acute ischemic stroke remain very limited [3, 4]. To date, there is no specifi
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