BACKGROUND: Thermogel is an aqueous solution that exhibits a sol-to-gel transition as the temperature increases. Stem cells, growth factors, and differentiating factors can be incorporated in situ in the matrix during the sol-to-gel transition, leading to the formation of a three-dimensional (3D) cell-culture scaffold. METHODS: The uses of thermogelling polypeptides, such as collagen, Matrigel™, elastin-like polypeptides, and synthetic polypeptides, as 3D scaffolds of cells, are summarized in this paper. RESULTS: The timely supply of growth factors to the cells, cell survival, and metabolite removal is to be insured in the cell culture matrix. Various growth factors were incorporated in the matrix during the sol-to-gel transition of the thermogelling polypeptide aqueous solutions, and preferential differentiation of the incorporated stem cells into specific target cells were investigated. In addition, modulus of the matrix was controlled by post-crosslinking reactions of thermogels or employing composite systems. Chemical functional groups as well as biological factors were selected appropriately for targeted differentiation of the incorporated stem cells. CONCLUSION: In addition to all the advantages of thermogels including mild conditions for cell-incorporation and controlled supplies of the growth factors, polypeptide thermogels provide neutral pH environments to the cells during the degradation of the gel. Polypeptide thermogels as an injectable scaffold can be a promising system for their eventual in vivo applications in stem cell therapy.
Biological Factors ; Cell Culture Techniques ; Cell Survival ; Collagen ; Equipment and Supplies ; Hydrogen-Ion Concentration ; Intercellular Signaling Peptides and Proteins ; Peptides ; Stem Cells

OBJECTIVE: Paclitaxel is one of the most effective antineoplastic drugs. HPV-related cervical lesions have only managed with invasive procedure. Topical drug administration with temperature sensitive copolymer gels are useful approaches to clinical situation. In this study, we evaluated the activity of multiblock copolymers of PEG/PLA (poly(L-lactic acid)/polyethylene glycol) gels with paclitaxel (PTX) formulation administered by topical treatment to mice bearing human cervical cancer cell lines (HeLa). METHODS: We have synthesized gels of PEG/PLLA (poly(L-lactic acid)/polyethylene glycol) multiblock copolymers containing Paclitaxel which have temperature-sensitivecharacteristics. This Paclitaxel-containg copolymers has the sol-gel-sol transition temperature at body temperature. The efficacy of PTX in PEG/PLA mutiblock copolymer micelle were conducted in HeLa-tumor bearing Balb/c Nu/Nu athymic mice at an equivalent paclitaxel dose of 10 mg/kg with 48 hr interval. The inhibition of tumor growth was evaluated after 8 days of treatment. Tumors were harvested at day 10 and stained with hematoxylin and eosine to measure tumor. RESULTS: PTX-containing PEG/PLA mutiblock copolymer significantly decreased tumor growth at day 8, as measured by tumor size; ie, PEG/PLA mutiblock copolymer only goup ; 1.43+/-0.26 m versus intraperitoneal treatment of Paclitaxel : 0.75+/-0.07 mm and topical treatment of PTX-containing PEG/PLA copolymer containing Paclitaxel : 0.28 mm (Min; 0.1 mm-Maxu0.8 mm). CONCLUSION: This demonstration that PTX-containing PEG/PLA mutiblock copolymer have a useful topical drug deliversy system carrying temperature sensitive characetersitics in HPV-related cervical lesions.
Administration, Topical ; Animals ; Antineoplastic Agents ; Body Temperature ; Cell Line ; Eosine Yellowish-(YS) ; Gels ; Hematoxylin ; Humans ; Lifting ; Mice ; Mice, Nude ; Models, Animal ; Paclitaxel ; Polymers ; Transition Temperature ; Ursidae ; Uterine Cervical Neoplasms