Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synovium removed from the knee of a 10-year-old with hemophilia A was characterized morphologically and biochemically. The specimen showed villous hypertrophy with hyperplasia of synovial lining cells which contained abundant intracytoplasmic granules of hemosiderin. Monolayer cultures prepared from enzymatically dispersed tissue were characterized by pigment-laden fibroblast-like cells and round cells. Both explants of synovium and adherent cells secreted a large amount of latent collagenase and neutral proteinase into the culture medium. The secretion of these enzymes dropped sharply and intracellular pigment decreased with passage of these cultures. Lysozyme was secreted by the explants but was not detected in the monolayer culture medium. These data establish the degradative potential of the synovitis found in hemophilia and support the concept that recurrent hemarthrosis without inflammation is sufficient in and of itself to produce proliferative synovitis.
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PMID:Proliferative synovitis in hemophilia: biochemical and morphologic observations. 62 83

Although protein replacement is an effective treatment for serum protein deficiencies such as diabetes and hemophilia, recombinant protein products are not available for all rare inherited diseases due to the instability of the recombinant proteins and/or to cost. Gene therapy is the most attractive option for treating patients with such rare diseases. To develop an effective ex vivo gene therapy-based protein replacement treatment requires recipient cells that differ from those used in standard gene therapy, which is performed to correct the function of the recipient cells. Adipose tissue is an expected source of proliferative cells for cell-based therapies, including regenerative medicine and gene transfer applications. Based on recent advances in cell biology and extensive clinical experience in transplantation therapy for adipose tissue, we focused on the mature adipocyte fraction, which is the floating fraction after collagenase digestion and centrifugation of adipose tissue. Proliferative adipocytes were propagated from the floating fraction by the ceiling culture technique. These cells are designated as ceiling culture-derived proliferative adipocytes (ccdPAs). We first focused on lecithin:cholesterol acyltransferase (LCAT) deficiency, an inherited metabolic disorder caused by lcat gene mutation, and ccdPAs as a therapeutic gene vehicle for LCAT replacement therapy. In our recent in vitro and animal model studies, we developed an adipose cell manipulation procedure using advanced gene transduction methods and transplantation scaffolds. We herein introduce the progress made in novel adipose tissue-based therapeutic strategies for the treatment of protein deficiencies and describe their future applications for other intractable diseases.
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PMID:Gene-manipulated Adipocytes for the Treatment of Various Intractable Diseases. 2715 Sep 23