NATURE: 26. 6. 2014

NATURE: Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells

"The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells1, 2, 3, holding promise for autologous cell replacement therapy4, 5. Although methods to induce pluripotent stem cells from somatic cells by transcription factors6 are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported7, 8, 9, 10, 11, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes."

http://www.nature.com/nature/journal/v510/n7506/full/nature13287.html

BLOOD: Loss of SPARC protects hematopoietic stem cells from chemotherapy toxicity by accelerating their return to quiescence

"Around birth, hematopoietic stem cells (HSCs) expanding in the fetal liver migrate to the developing bone marrow (BM) to mature and expand. To identify the molecular processes associated with HSCs located in the 2 different microenvironments, we compared the expression profiles of HSCs present in the liver and BM of perinatal mice. This revealed the higher expression of a cluster of extracellular matrix-related genes in BM HSCs, with secreted protein acidic and rich in cysteine (SPARC) being one of the most significant ones. This extracellular matrix protein has been described to be involved in tissue development, repair, and remodeling, as well as metastasis formation. Here we demonstrate that SPARC-deficient mice display higher resistance to serial treatment with the chemotherapeutic agent 5-fluorouracil (5-FU). Using straight and reverse chimeras, we further show that this protective effect is not due to a role of SPARC in HSCs, but rather is due to its function in the BM niche. Although the kinetics of recovery of the hematopoietic system is normal, HSCs in a SPARC-deficient niche show an accelerated return to quiescence, protecting them from the lethal effects of serial 5-FU treatment. This may become clinically relevant, as SPARC inhibition and its protective effect on HSCs could be used to optimize chemotherapy schemes."

http://bloodjournal.hematologylibrary.org/content/123/26/4054?sso-checked=1