In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads.

Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

Stem cells--a clinical update.

BACKGROUND: Stem cells of adult origin have been used clinically for 40 years in the treatment of haematological neoplasms such as leukaemia. These cells were originally obtained from bone marrow, but are now also being derived from umbilical cord blood. OBJECTIVE: With the increasing public awareness of stem cell use, general practitioners need to be aware for which disorders these cells can, and are, being used. DISCUSSION: Recent clinical trials with stem cells have been for ischaemic heart disease and to assist nonunion of bone. Other adult stem cells used in clinical trials include olfactory cells for spinal cord lesions, and human fetal pancreatic cells for type 1 diabetes. Adult stem cells, however, have limited potential to differentiate into different cell types. Human embryonic stem cells can be converted into cells of all lineages. They first became available for research in 1998 but are yet to be used in clinical trials.