Mesenchymal stem cell therapy for halting the progression of acute and chronic kid...
| Grant number: | 13/19560-6 |
| Support type: | Regular Research Grants |
| Duration: | August 01, 2014 - January 31, 2017 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Érika Bevilaqua Rangel |
| Grantee: | Érika Bevilaqua Rangel |
| Home Institution: | Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil |
| Assoc. researchers: | Joshua M Hare ; Samirah Abreu Gomes |
Abstract
Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all age, racial and ethnic groups. CKD is incurable, requiring renal replacement therapy, that is, dialysis or renal transplantation. Identification of stem cell populations in mammalian tissues is therefore important for therapeutic applications and for understanding developmental processes and tissue homeostasis. Our group recently reported that c-kit+ cells isolated from developing rat kidneys exhibit stem cell properties and regenerate epithelial tubular cells following ischemia-reperfusion injury. We hypothesize that c-kit+ cells represent a tissue-specific stem cell population that contribute either to nephron formation during kidney development or tissue homeostasis, are maintained during adult life, and have therapeutic potential. Lineage tracing will be performed by crossing the inducible c-kit Cre reporter mice with the IRG (insulator/red/green) and Rosa26 reporter lacZ mice. By varying the timing of tamoxifen treatment and therefore Cre-mediated recombination, c-kit+ cells and their descendents will be specifically labeled with enhanced green fluorescent protein (EGFP) or lacZ and their location/migration will be followed. We anticipate finding individual c-kit+ cells activated within the nascent nephrons in the cortex and as the kidney develops, these undifferentiated c-kit+ cells expand to form tubular structures extending from the cortex into the medulla. Ex vivo culture of embryonic mouse kidneys are expected to recapitulate the spatiotemporal changes in c-kit-EGFP expression during embryonic kidney development. To verify if c-kit+ cells maintain renal homeostasis, we will analyze their proliferation in response to tissue damage following ischemia-reperfusion injury in the c-kit Cre reporter mice. Next, we will document if human kidneys harbor a tissue-specific c-kit+ stem cell population that have therapeutic potential. Therefore we will isolate kidney-derived human c-kit+ cells and characterize their stem cell properties by assessing clonogenicity, self-renewal capacity, multipotentiality, and their regenerative potential following ischemia-reperfusion injury in immune compromised mice. Taken together, our goal is to document that cross-species conservation exists and that c-kit+ cells correspond to a kidney-specific population of stem cells that have important biological and therapeutic properties. (AU)