Preparation of agarose coated, solid agarose 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]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. 10 / 336,442, filed Jan. 2, 2003, which is a divisional of reissue application Ser. No. 09 / 345,196, filed Jun. 30, 1999, now U.S. Reissue 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.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., insulin), growth factors, cytokines, and so forth. Their rol...

AI Technical Summary

Benefits of technology

"The present invention provides a method for producing three types of secretory cell macrobeads that can be used to treat conditions caused by impaired functioning of the host's secretory cells. These macrobeads can be stored for long periods of time and are effective in treating patients with conditions characterized by an insufficiency in a secretory cell product. The invention also provides a method for preserving secretory cells by forming and incubating these macrobeads."

Problems solved by technology

The clinical application of pancreatic islet transplantation have been limited by 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 fibroptic 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.

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.

Images