Preparation of agarose coated, solid agarose-collagen beads containing secretory cells

Abstract

Biological agents such as secretory cells are encapsulated in a hydrophilic gel made of agarose or collagen-agarose and gelatin sponge-agarose combinations. In a preferred embodiment, semi-solid beads are formed from a suspension containing collagen, agarose and secretory cells such as pancreatic islets, the collagen is polymerized to form solid, agarose-collagen beads and the solid beads are coated with agarose. Coating is preferably by rolling the solid beads in about 5-10% agarose, contacting the rolled beads with mineral oil and washing oil from the beads. Beads containing secretory cells can be transplanted into a mammal to treat a condition caused by impaired secretory cell function.

Description

[0001]Notice: More than one reissue application has been filed for the reissue of U.S. Pat. No. 5,643,569. This application is a divisional of reissue application Ser. No. 09 / 345,196, filed Jun. 30, 1999, now U.S. Reissued Pat. No. RE 38,027 E, which is a reissue of application Ser. No. 08 / 483,728, filed Jun. 7, 1995, now U.S. Pat. No. 5,643,569, which is a continuation of application Ser. No. 08 / 181,269 filed Jan. 13, 1994, now abandoned. Reissue application Ser. No. 10 / 979,527, filed Nov. 1, 2004 is a divisional of reissue application Ser. No. 10 / 336,442, filed Jan. 2, 2003.FIELD OF THE INVENTION[0002]The present invention relates to macroencapsulation of secretory cells in a hydrophilic gel material, therapeutic methods employing the macroencapsulated secretory cells, and preserving the secretory cells by macroencapsulation.BACKGROUND OF THE INVENTION[0003]Secretory cells are cells that are characterized by secreting biological products, such as, but not limited to, hormones (e.g...

AI Technical Summary

Benefits of technology

[0016]It is therefore an object of the present invention to provide a secretory cell macrobead that can be transplanted into animals to treat conditions caused by an impaired functioning of the host's secretory cells.

[0017]It is a further object of this invention to provide a secretory cell macrobead that can be stored for long lengths of time.

Problems solved by technology

The clinical applications of pancreatic islet transplantation have been limited to the inability to prevent islet allograft-xenograft rejection, i.e., a rejection of the transplanted pancreatic islets due to the host's immune system attacking the transplanted pancreatic islets.

Immunosuppressive therapy, however, has proved to be a double-edged sword; while reducing the risk of rejection, it impairs the body's overall immunological defenses.

As discussed below, although temporary success has been reported (See hey, Diabetes Reviews 1 (1):76 (1993), effective long-term methods have yet to be achieved.

All of these methods have failed, however, due to one or more of the following problems; a host fibrotic response to the implant material, instability of the implant material, limited nutrient diffusion across semi-permeable membranes, secretagogue and product permeability, and diffusion lag-time across semi-permeable membrane barriers.

Other investigators, however, repeating these experiments, found the alginate to cause a tissue reaction and were unable to reproduce Lira et al's results (Lamberti, et al., Applied Biochemistry and Biotechnology 10:101 (1984); Dupuy, et al., Jour. Biomed. Material and Res. 22:1061 (1988); Weber, et al.

Their method, however, suffers from a number of drawbacks.

It is cumbersome and inaccurate.

Furthermore, the transplanted beads are difficult to retrieve, tend to be fragile, and will easily release islets upon slight damage.

They found that when the islets are injected into the fiber, they aggregate within the hollow tube and result in necrosis in the central portion of the islet masses.

However, this experiment has not been extensively repeated.

Therefore, the membrane's function as an islet transplantation medium in humans is questionable.

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