Faculty Bibliography

The limited ability of cardiac muscle to regenerate after an extensive myocardial infarction (MI) and the scarcity of cardiac donors have fueled the field of cardiac tissue engineering as a potential therapeutic approach to enhance cardiac function in post-MI patients. We are exploring the ex vivo bioengineering of cardiac muscle tissue by seeding isolated cardiac cells within alginate scaffolds and supplementing the culture with "smart" media. The hypothesis investigated herein is that sera derived from autospecies and from post-MI animals contain agents that might induce cell proliferation, survival, and maturation in vitro. The results of the metabolic activity of the neonatal cardiac cell constructs (6.4-51x10(6) cells/cm(3)), as measured by MTT viability assay, indicated a significant advantage (p < 0.05) to the constructs supplemented with serum from normal and post-MI adult rats compared to fetal calf serum (FCS) supplementation. H&E staining and alpha-sarcomeric actin immunofluorescence staining revealed thick viable cardiac cell clusters (150-300 microm), with abundant 3D architecture in the cardiac cell constructs supplemented with post-MI and normal adult rat serum. The number of cells positively immunostained with Ki-67, a cell proliferation marker, was significantly higher in post-MI adult rat serum-supplemented cultures compared to negative results in the FCS-supplemented culture. The results presented in this study indicate that media supplemented with post-MI adult rat serum and normal adult rat serum compared to FCS have a significant advantage in the regeneration of injured cardiac tissue.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease, which is characterized by recurrent episodes of fever, anhidrosis, self mutilation, absence of reaction to noxious stimuli, prolonged healing times and mental retardation. The absence of pain sensation combined with mental retardation predisposes the children to recurrent wound infections and deep ulcers that heal at a slower pace than seen in healthy people. The anomalous pain is due to the absence of dorsal root ganglia that are responsible for pain sensation and absence of afferent neurons activated by tissue damaging stimuli. Nerve Growth Factor (NGF) is a growth factor that supports the survival of nociceptive sensory and autonomic sympathetic neurons. Neurotrophin Tyrosine Receptor (NTRK1) encodes a receptor tyrosine kinase that is activated in response to NGF. NTRK1 mutations have been found in mice that presented with clinical signs similar to CIPA, subsequently CIPA patients have been examined for these mutations as well. Currently, 37 different mutations at the NTRK1 are known which cause CIPA. The above syndrome is so rare that until the year 2000 only 84 cases have been reported, not including 28 known cases of CIPA patients from Israeli Bedouins. Since no cure is available, prenatal screening, as conducted in our institution, is the only available preventive option to avoid the birth of an affected child.