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The Edmond and Lily Safra Children's Hospital
Pediatric Stem Cell Research Institute

Benjamin Dekel, MD, PhD, Head (Read More)

Binyamin.Dekel@sheba.health.gov.il

Generation of new vessels in the injured kidney following injection of bone-marrow derived stem cells (Click on photo's to enlarge)

 

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Aims:

Our overall goal is to create a bridge between basic science discoveries and translational research so as to develop novel remedies for pediatric incurable disease.

Specific Amis:

(i) To translate basic findings in stem cell research to applications of cell therapy and regenerative medicine, especially for cure of renal diseases.

(ii) To develop novel therapeutics against cancer via targeting of cancer stem cells.

(iii) To develop a research environment that would promote interactions between pediatric clinicians and scientists and nurture physician-scientists.

Research Activities:

(i) Isolation and characterization of tissue-specific human kidney stem cells for the treatment of renal disease

(ii) Isolation and characterization of human kidney cancer stem cells for the targeted therapy of renal cancer

(iii) Isolation and characterization of endothelial progenitor cells for the treatment of diseases associated with vascular pathologies

Scientific Abstract:

Stem cells are what all cells from all organs, tissues etc. existed as in the very beginning of their lives. Stem cells can self-renew, meaning during cell division it creates a copy of itself which is identical in every aspect and is a primitive, undifferentiated stem cell just like the one it arose from. The other cell progeny is a daughter cell that has the genes to code for proliferation, meaning it will grow and mature until it becomes the specialized cell that it is destined to become. There are diverse array of stem cells including embryonic stem cells, which have the total potential to become an entire organism. Theoretically, embryonic stem cells can give rise to every single cell type in the body, whether it be a heart cell (cardiomyocyte), a liver cell (hepatocyte), a brain cell (neuron or glial cell), or a blood cell (red and white blood cells). Beyond this point, there are more compartmentalized stem cells like a hematopoietic stem cell, which eventually evolves into all cell types of the hematopoietic system. This type of stem cell is referred to as tissue-specific stem cell, which is still a stem cell but possesses some bias as to what cell it will form and it tends to replenish mature specialized cells of organs and tissues in which itself resides in. While tissue-specific stem cells have been recently identified in several organs (brain, heart, skin), kidney stem cells are yet to be identified and located.

Chronic kidney disease (CKD) means that that the kidney are now working properly, leading to a slow build up of waste products and fluids in the body. When the kidneys are more severely affected and near the end of their function (less than 10% of the normal) the stage of chronic kidney disease may be called end stage renal disease (ESRD). At this stage the build up of waste products increases to the point that health is severely affected and dialysis and/or kidney transplantation are necessary to replace kidney function.The progression of CKD is often relentless with the majority of patients reaching end-stage renal disease.

Identification of multipotential progenitor populations in mammalian tissues is important both for therapeutic potential and an understanding of developmental processes and tissue homeostasis. Progenitor populations are ideal targets for gene therapy, cell transplantation, and tissue engineering of bioartificial organs. A demand for kidney progenitors is increasing because of a severe shortage of donor organs for orthotopic kidney transplantation. Because dialysis and kidney transplantation currently are the only successful therapies for patients suffering chronic renal failure, cell therapy with renal progenitor cells offers an alternative approach for therapies of kidney diseases. Nevertheless, this approach may be relevant only in earlier stages of chronic kidney disease, when residual kidney function and kidney histology are still preserved, allowing for the integration of cells and not when small and fibrotic end-stage kidneys develop. While blood and bone marrow derived stem cells (hematopoietic and mesenchymal stem cells) hold a potential for therapeutic usage, so far they have been found to be minimally effective in renal disease, emphasizing the need to seek kidney stem cells beyond the known extra-renal sources.

A major source for derivation of renal stem cells is the fetal kidney. Nephrogenesis within the fetal kidney takes place in a discrete anatomic compartment termed the nephrogenic mesenchyme which is comprised of self-renewing stem cells that give rise to all cell types of the nephron, the functional unit of the kidney, and may prove valuable for renal regeneration after their isolation. Renal stem cells are induced to form nephrons until 34 weeks of gestation. For renal regeneration, both human embryonic kidney precursor tissue and fetal kidney cell transplantation can be utilized. Nevertheless, isolation of specific human renal stem cells from their discrete anatomic compartment requires the characterization of surface markers that would enable cell collection. Over the past few years a comprehensive effort using DNA chips, FACS analysis and immunostaining has enabled us to characterize a combination of cell surface markers the expression of which correspond to early renal developmental stages, including cells that comprise the nephrogenic mesenchyme and are therefore putative renal stem cells. We are now at a stage where such cells can be readily retrieved from human fetal kidneys according to their surface markers and tested in pre-clinical animal models of progressive renal disease, a condition that mimics CKD in humans, so as to determine whether they have the potential to halt CKD. Thus, we aim to translate our basic findings into applicative research that if found promising will have great impact on renal medicine.

 

Financial Resources


  • ISRAEL SCIENTIFIC FOUNDATION
  • ISRAEL CANCER RESEARCH FOUNDATION
  • WOLFSON CLORE MAYER
  • 'NOFAR' MINISTRY OF INDUSTRY
  • MINISTRY OF HEALTH

  • ISRAEL CANCER FOUNDATION

  • SHRIBER AND BRETLER FOUNDATIONS, TAU

 

 

 

 

 

 

STEM CELLS IN THE DEVELOPING HUMAN KIDNEY


(Click on photo's to enlarge)

 
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