Biomedical subjects

Craig Halberstadt

Publications and source records attributed to Craig Halberstadt.

5 recordsLinked to original sources

PubMed2006

Combining cell therapy and nanotechnology.

Cell transplantation to treat diseases characterised by tissue and cell dysfunction, ranging from diabetes to spinal cord injury, has made great strides preclinically and towards clinical efficacy. In order to enhance clinical outcomes, research needs to continue in areas including the development of a universal cell source that can be differentiated into specific cellular phenotypes, methods to protect the transplanted allogeneic or xenogeneic cells from rejection by the host immune system, techniques to enhance cellular integration of the transplant within the host tissue, strategies for in vivo detection and monitoring of the cellular implants, and new techniques to deliver genes to cells without eliciting a host immune response. Overcoming these obstacles will be of considerable benefit, as it allows understanding, visualising and controlling cellular interactions at a submicron level. Nanotechnology is a multidisciplinary field that allows us to manipulate materials, tissues, cells and DNA at the level of and within the individual cell. As such, nanotechnology may be well suited to optimise the generally encouraging results already achieved in cell transplantation. This review presents some of the ways that nanotechnology can directly contribute to cell transplantation.

Animals↗

PubMed2005

Sertoli cells improve survival of motor neurons in SOD1 transgenic mice, a model of amyotrophic lateral sclerosis.

Cell replacement therapy has been widely suggested as a treatment for multiple diseases including motor neuron disease. A variety of donor cells have been tested for treatment including isolated preparations from bone marrow and embryonic spinal cord. Another cell source, Sertoli cells, have been successfully used in models of diabetes, Parkinson's disease and Huntington's disease. The ability of these cells to secrete cytoprotective proteins and their role as 'nurse cells' supporting the function of other cell types in the testes suggest their potential use as neuroprotective cells. The current study examines the ability of Sertoli cells injected into the parenchyma of the spinal cord to protect motor neurons in a mouse model for amyotrophic lateral sclerosis. Seventy transgenic mice expressing the mutant (G93A) human Cu-Zn superoxide dismutase (SOD1) received a unilateral spinal injection of Sertoli-enriched testicular cells into the L4-L5 ventral horn (1 x 10(5) cells total) prior to the onset of clinical symptoms. The animals were euthanized at the end stage of the disease. Histological and morphometric analyses of the transplant site were performed. A significant increase in the number of surviving ChAT positive motor neurons was found ipsilateral to the injection compared with contralateral and uninjected spinal cord. The ipsilateral increase in motor neuron density was dependent upon proximity to the injection site. Sections rostral or caudal to the injection site did not display a similar difference in motor neuron density. Implantation of a Sertoli-cell-enriched preparation has a significant neuroprotective benefit to vulnerable motor neurons in the SOD1 transgenic model. The therapeutic benefit may be the result of secreted neurotrophic factors present at a critical stage of motor neuron degeneration in this model.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Use of Sertoli cell transplants to provide local immunoprotection for tissue grafts.

The recent success of allogeneic islet transplantation for the treatment of type I diabetes has renewed interest in cell therapy for diseases of secretory cell dysfunction. Unfortunately, widespread clinical use of cell transplantation is limited by tissue availability and the need for long-term immunosuppresion. Testicular Sertoli cells can confer local immunoprotection for co-transplanted cells and may provide a means of overcoming the obstacles associated with cell transplantation. Sertoli cell grafts protect islets in animal models of diabetes and can be transplanted into the brain to enhance regeneration and promote the survival of co-grafted tissues. This review describes the role that Sertoli cells normally play in testicular immunology, details the preclinical data using transplanted Sertoli cells in models of diabetes and Parkinson's disease and discusses some of the possible mechanisms involved in this phenomena, as well as the future of this technology.

Animals↗

PubMed2003

Long-term survival of intratesticular porcine islets in nonimmunosuppressed beagles.

BACKGROUND: The testis is an immunoprivileged organ, and at 37 degrees C, the intratesticular microenvironment supports the survival of allogeneic islets. The objective of this study was to determine whether the immunoprotection afforded by the intratesticular environment is potent enough to prevent the rejection of xenogeneic porcine islets in a large-animal model. METHODS: A bilateral cryptorchid condition was surgically created in sexually mature beagle dogs. Porcine islets were prepared from neonatal pigs by collagenase digestion and 9 days of culture, after which they were injected into each of the cryptorchid testes. Control dogs received liver subcapsular space transplants of porcine islets and autologous islets. After 100 days, the testes and relevant portions of liver were studied immunohistochemically for the presence of islet tissue. RESULTS: The testicular interstitial space of all dogs contained abundant islet tissue. No evidence of lymphocytic infiltration or inflammation was observed. In contrast, porcine islets transplanted to the liver subcapsular space do not survive, although autologous islets engraft well in that position. This occurs even though the recipient's serum contains preformed cytotoxic antibodies to porcine islets that persist after transplantation. CONCLUSIONS: These results demonstrate that the microenvironment existing within the surgically repositioned intra-abdominal testis supports the survival of xenogeneic tissue. The survival of xenogeneic tissue in the absence of immunosuppression in this large-animal model raises the possibility that xenogeneic porcine islet tissue will also survive in humans if transplanted into a similar environment.

Animals↗

PubMedDate not supplied

Synthesis, characterization, and preliminary biological study of poly(3-(tert-butoxycarbonyl)-N-vinyl-2-pyrrolidone).

Poly(3-(tert-butoxycarbonyl)-N-vinyl-2-pyrrolidone) has been synthesized and characterized by gel permeation chromatography, Fourier transform infrared spectroscopy, NMR spectroscopy, and thermal analysis. The polymer is a chemically amplified photoresist. Arrays of lines with 25 microm width and 25 microm spacing were successfully patterned with this polymer by photolithography. Rat fibroblast cells were seeded on these patterned surfaces as well as the smooth glass surface. Phase contrast microscopy showed that cells on the patterned surfaces were strongly aligned and elongated along the grooves as compared to randomly spreading on the smooth surface. Since controlling cell orientation is critical for the development of advanced forms of tissue repair and cell engineering therapies, for example, peripheral nerve repair, production of tendon and ligament substitutes in vitro, and control of microvascular repair, the described polymer may be useful for applications in tissue reconstruction.

Animals↗