Extracellular matrix induction method to produce pancreatic isle

Surgery – Blood vessel or graft preparation

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128898, 435 1, A61B 1900

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049350005

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BRIEF SUMMARY
BACKGROUND OF THE INVENTION

Embryonic development of the pancreas involves an epithelial endoderm budding from the primitive gut tube into surrounding mesenchyme (splanchnic mesoderm). The process is described in detail in the publication by R. Pictet and W. Rutter, HANDBOOK OF PHYSIOLOGY, Vol. 1, Section 7, Endocrinology: Endocrine Pancreas, D. Steiner and N. Freinkel, eds., Amer. Physiol. Soc. L972, pp. 25-66. The sequential epithelial/mesenchymal interactions results in the formation of both exocrine and endocrine pancreas. Later in adult life, it is believed that very little endocrine neogenesis occurs in the pancreas. This has led to the conclusion of some investigators in the diabetes field to consider the beta cell (the beta cell is the source cell for insulin) a "terminal" cell. A terminal cell is a fully differentiated cell that exhibits very little mitosis in adult life, and consequently, at birth, an individual has the full complement of these cells. The terminal nature of the beta cell has far reaching implications in the field of diabetes since beta cell destruction or functional impairment results in a devastating clinical situation without any hope of new, healthy, beta cell formation occurring to alleviate the disease.
In the past, many investigators have studied the effects of various conditions on the mitotic activity of pre-existing beta cells in the pancreas. These conditions have included the effect of diet, hormones, partial pancreatectomy, diabetogenic chemicals, genetic manipulation, sulfonylureas, insulin antibody, glucose, and amino acids. See, for example, J. Logothetopoulos, HANDBOOK OF PHYSIOLOGY, Vol. 1, Section 7, Endocrinology: Endocrine Pancreas, D. Steiner and N. Freinkel, eds., Amer. Physiol. Soc. 1972, pp. 67-76. The crux of these studies has been to increase the mitotic activity of pre-existing beta cells. None of these studies has dealt with the concept of the neoformation or regeneration of islet beta cells from non-islet entities (islets are groups of beta cells).
Many investigators have found that in vitro culture of fetal pancreas exhibits a high rate of beta cell mitosis and also some evidence of neoformation of beta cells from "budding islets" which seems to result from true neogenetic process (morphogenesis and histogenesis); et al., Morphological Study of Cultured Pancreatic Fetal Islets: Diabetes, Vol. 29, Jan. 1980, pp. 16-21. In addition, Archer and Jai (U.S. Pat. No. 4,439,521; Mar. 27, 1984; Method for Producing Self-Reproducing Mammalian Pancreatic Islet-like Structures) describe a method for producing pancreatic islet-like structures using in vitro culturing techniques. They have been able to increase islet tissue using standard tissue culture technology of pancreatic islets, pancreatic duct pieces, cell clusters of pancreas, cell tissues obtained as by products of the culturing method, or previously produced islet-like structures.
The invention of this application relates to a method and composition for regenerating cells in a post natal subject, cells which do not normally regenerate apart from fetal development. Specifically, islet cells of the pancreas may be regenerated.


SUMMARY OF THE INVENTION

In accordance with this invention, a method is provided which comprises implanting into a living subject an effective amount of fetal mesenchyme cells of a type and age capable of eliciting a desired biological response from other fetal cells. As the result of such implantation, the biological response is elicited in the cells of the living subject. Thus, by this method, cells in the body of an adult may be stimulated by the implantation of the proper mesenchyme cells to behave in a manner which is abnormal for adult cells, but which is typical behavior for precursor cells to those adult cells in the fetus. By this technique, desired growths and transformations of living adult cells can take place in a manner which is analogous to fetal growth; specifically, the process involves reawakening dormant adult "precursor" epithelial cells by use of temporally

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