Search PubMed⌕ Search

Biomedical subjects

Marc R Hammerman

Publications and source records attributed to Marc R Hammerman.

28 records · Page 2Linked to original sources
PubMed2003

Tissue engineering the kidney.

The means by which kidney function can be replaced in humans include dialysis and renal allotransplantation. Dialytic therapies are lifesaving, but often poorly tolerated. Transplantation of human kidneys is limited by the availability of donor organs. During the past decades, a number of different approaches have been applied toward tissue engineering the kidney as a means to replace renal function. The goals of one or another of them included the recapitulation of renal filtration, reabsorptive and secretory functions, and replacement of endocrine/metabolic activities. This review will delineate the progress to date recorded for five approaches: (1) integration of new nephrons into the kidney; (2) growing new kidneys in situ; (3) use of stem cells; (4) generation of histocompatible tissues using nuclear transplantation; and (5) bioengineering of an artificial kidney. All five approaches utilize cellular therapy. The first four employ transplantation as well, and the fifth uses dialysis.

Animals↗
PubMed2003

Therapeutic promise of embryonic kidney transplantation.

One novel solution to the shortage of human kidneys available for transplantation envisions 'growing' new kidneys in situ via xenotransplantation of renal anlagen. We and others have shown that developing metanephroi transplanted into animal hosts undergo differentiation and growth, become vascularized by blood vessels of host origin and exhibit excretory function. Metanephroi can be stored for up to 3 days in vitro prior to transplantation with no impairment in growth or function post-implantation. Metanephroi can be transplanted across both concordant (rat to mouse) and discordant/highly disparate (pig to rodent) xenogeneic barriers. Here we review studies exploring the potential therapeutic use of embryonic kidney transplantation.

Animals↗
PubMed2002

Fibroblast growth factor 2 promotes microvessel formation from mouse embryonic aorta.

To delineate the roles that oxygen and fibroblast growth factors (FGFs) play in the process of angiogenesis from the embryonic aorta, we cultured mouse embryonic aorta explants (thoracic level to lateral vessels supplying the mesonephros and metanephros) in a three-dimensional type I collagen gel matrix. During 8 days of culture under 5% O(2), but not room air, the addition of FGF2 to explants stimulated the formation of Gs-IB(4-)positive, CD31-positive, and Flk-1-positive microvessels in a concentration-dependent manner. FGF2-stimulated microvessel formation was inhibited by sequestration of FGF2 via addition of soluble FGF receptor (FGFR) chimera protein or anti-FGF2 antibodies. FGFR1 and FGFR2 were present on explants. Levels of FGFR1, but not FGFR2, were increased in embryonic aorta cultured under 5% O(2) relative to room air. Our data suggest that low oxygen upregulates FGFR1 expression in embryonic aorta in vitro and renders it more responsive to FGF2.

Animals↗
PubMed2002

Transplantation of embryonic kidneys.

The number of kidney allotransplants performed per year is limited by the availability of human donor organs. Xenotransplantation of a vascularized organ, such as the kidney, as an alternative to allotransplantation presents formidable immunological challenges. One novel solution to this conundrum is to use embryonic kidneys taken from animal donors early during organogenesis when metanephroi can be transplanted in 'cellular' form. We and others have shown that developing embryonic kidneys (metanephroi) transplanted into the omentum of animal hosts undergo differentiation and growth in situ, become vascularized by blood vessels of host origin and exhibit excretory function. Metanephroi can be stored for up to 3 days in vitro prior to transplantation with no impairment in growth or function post-implantation. Metanephroi can be transplanted across both concordant (rat to mouse) and highly disparate/discordant (pig to rodent) xenogeneic barriers. This review summarizes experimental data relating to the transplantation of embryonic kidneys.

Animals↗
PubMed2002

Xenotransplantation of renal primordia.

The limited availability of donor organs restricts the number of kidney transplantations performed per year. One novel solution to this shortage envisions 'growing' new kidneys in situ via xenotransplantation of renal primordia. To be successful, such an approach would require the following criteria to be met: that transplants are 'grown' in a location that renders their subsequent excretory function possible; that developed transplants have normal morphology and function; that transplanted metanephroi become well integrated into the host, in terms of inducing a state of immune tolerance and being vascularized by host vessels; and that source material for metanephros transplants is easy to access. This review summarizes recent work addressing these issues.

Animals↗
PubMed2002

Microvessel formation from mouse embryonic aortic explants is oxygen and VEGF dependent.

To delineate the roles of O(2) and vascular endothelial growth factor (VEGF) in the process of angiogenesis from the embryonic aorta, we cultured mouse embryonic aorta explants (thoracic level to lateral vessels supplying the mesonephros and metanephros) in a three-dimensional type I collagen gel matrix. During 8 days of culture under 5% O(2), but not room air, the addition of VEGF to explants stimulated the formation of CD31-positive, Flk-1-positive, Gs-IB(4)-positive structures in a concentration-dependent manner. Electron microscopy showed the structures to be capillary-like. VEGF-induced capillary-like structure formation was inhibited by sequestration of VEGF via addition of soluble Flt-1 fusion protein or anti-VEGF antibodies. Expression of Flk-1, but not Flt-1, was increased in embryonic aorta cultured under 5% O(2) relative to room air. Our data suggest that low O(2) upregulates Flk-1 expression in embryonic aorta in vitro and renders it more responsive to VEGF.

Animals↗
PubMed2002

Xenotransplantation of developing kidneys.

The number of kidney transplants performed per year is limited by the availability of donor organs. One novel solution to this shortage envisions "growing" new kidneys in situ via xenotransplantation of renal anlagen. We have shown that developing metanephroi transplanted into the omentum of animal hosts undergo differentiation and growth, become vascularized by blood vessels of host origin, and exhibit excretory function. Metanephroi can be stored for up to 3 days in vitro before transplantation with no impairment in growth or function postimplantation. Metanephroi can be transplanted across both concordant (rat --> mouse) and discordant/highly disparate (pig --> rodent) xenogeneic barriers. This review summarizes experimental data relating to the transplantation of developing kidneys.

Animals↗
PubMedDate not supplied

Transplantation of pig metanephroi.

To determine whether pig metanephroi grow and differentiate after allotransplantation or xenotransplantation across a highly disparate barrier, we implanted metanephroi from embryonic day 28 (E28) pig embryos into the omentum of unilaterally nephrectomized adult pigs or C57Bl/6J mice (hosts). Some mouse hosts received anti-CD45RB, anti-CD154, and anti-CD11a (costimulatory blockade). E28 pig metanephroi were < 0.2 mm in diameter and contained only metanephric blastema and segments of ureteric bud. Pig metanephroi transplanted into pigs underwent growth and differentiation of nephrons over a 2 week period without the need for costimulatory blockade of hosts. In contrast, pig metanephroi did not grow or differentiate in mice that received no costimulatory blockade. However, by 2 weeks posttransplantation in mice in which costimulation was blocked, metanephroi from E28 pigs had enlarged, become vascularized, and had formed mature tubules and glomeruli. By 3 weeks posttransplantation in mice, metanephroi had grown to the point that they were approximately half the volume of the native mouse kidney. Here we show that growth and development of pig metanephroi occurs posttransplantation across an allogeneic or highly disparate xenogeneic barrier.

Animals↗
PubMedDate not supplied

Intraperitoneal transplantation of pancreatic anlagen.

To determine whether embryonic pancreatic anlagen transplanted to an intraperitoneal site in adult hosts grow, differentiate, and function, we implanted pancreas from embryonic day (E) 12.5 Lewis rat embryos into the omentum of adult Lewis rats or C57Bl/6J mice. E12.5 pancreatic anlagen were relatively undifferentiated except for the presence of condensing tubuloacinar cords. By 2 weeks after implantation, pancreatic anlagen transplanted into rats had enlarged and differentiated such that islets of Langerhans that stained positive for insulin could be delineated. Continued differentiation, as reflected by the presence of "ductal" islets connected to the duct epithelium, was observed at 6 weeks after implantation. At 15 weeks after implantation, "mature" islets had separated from the ducts. Electron microscopy showed eccentric dense bodies within clear vacuoles consistent with insulin granules. Little or no acinar tissue was present in developed anlagen. Within 5 weeks of pancreatic anlagen transplantation, levels of glucose in rats rendered diabetic by an injection of streptozotocin were normalized compared with levels in nontransplanted diabetic controls. Rat pancreatic anlagen underwent growth and development in the peritoneum of C57Bl/61 mice that received costimulatory blocking agents but not in the absence of costimulatory blockade. We concluded that whole E12.5 pancreatic anlagen undergo growth, differentiation, and function after intraperitoneal placement. Implantation of the embryonic pancreas, a "cellular" transplant, is followed by selective differentiation of islet compared with acinar components.

Animals↗