Optimization of alginate encapsulation of islets for transplantation

Abstract

Apparatus is provided, including a plurality of islets, and a hydrogel configured to macroencapsulate the plurality of islets. The hydrogel is implantable in a subcapsular space ( 21 ) of a kidney ( 22 ) of a subject and is shaped to define a planar configuration. Other applications are also described.

1 . Apparatus, comprising:
 a plurality of islets; and   a hydrogel configured to macroencapsulate the plurality of islets, the hydrogel being implantable in a subcapsular space of a kidney of a subject, and shaped to define a planar configuration.   
     
     
         2 . The apparatus according to  claim 1 , further comprising at least one semi-permeable membrane covering at least a portion of the hydrogel. 
     
     
         3 . The apparatus according to  claim 1 , wherein the plurality of cells has a density of 2,000-8,000 islets/cm̂2. 
     
     
         4 . The apparatus according to  claim 1 , further comprising at least one semi-permeable membrane disposed at least in part within at least a portion of the hydrogel. 
     
     
         5 . The apparatus according to  claim 1 , wherein the hydrogel is configured to be implanted in the subcapsular space of the kidney using laparoscopy. 
     
     
         6 . The apparatus according to  claim 1 , wherein the hydrogel is configured to be removed from the subcapsular space of the kidney using laparoscopy. 
     
     
         7 . The apparatus according to  claim 1 , wherein the hydro gel comprises constituents of extracellular matrix. 
     
     
         8 . The apparatus according to  claim 1 , wherein the hydrogel comprises collagen. 
     
     
         9 . The apparatus according to  claim 1 , wherein the hydrogel comprises laminin. 
     
     
         10 . The apparatus according to  claim 1 , wherein the hydrogel comprises mesenchymal stem cells. 
     
     
         11 . The apparatus according to  claim 1 , wherein the plurality of islets comprises 80,000-4,000,000 islets. 
     
     
         12 . The apparatus according to  claim 11 , wherein the plurality of islets comprises 200,000-800,000 islets. 
     
     
         13 . The apparatus according to  claim 1 , wherein the hydrogel comprises alginate, and wherein the alginate has a concentration of guluronic acid of between 30% and 50%. 
     
     
         14 . The apparatus according to  claim 13 , wherein the concentration of guluronic acid is between 40% and 47%. 
     
     
         15 . The apparatus according to  claim 13 , wherein the alginate has a dry matter content of at least 1.6%. 
     
     
         16 . The apparatus according to  claim 13 , wherein the alginate has a dry matter content of at least 2.1%. 
     
     
         17 . The apparatus according to  claim 13 , wherein the alginate is cross-linked with strontium. 
     
     
         18 . A method, comprising:
 providing a plurality of islets macroencapsulated in a hydro gel shaped to define a planar configuration; and   implanting the macroencapsulated islets in a subcapsular space of a kidney of a subject.   
     
     
         19 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydro gel that is covered at least in part by a semi-permeable membrane. 
     
     
         20 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel and in a semi-permeable membrane that is disposed at least in part within the hydrogel. 
     
     
         21 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises providing a plurality of islets having a density of 2,000-8,000 islets/cm̂2. 
     
     
         22 . The method according to  claim 18 , wherein implanting the macroencapsulated islets in the subcapsular space of the kidney comprises implanting the macroencapsulated islets in the subcapsular space of the kidney using laparoscopy. 
     
     
         23 . The method according to  claim 18 , further comprising removing the macroencapsulated islets from the subcapsular space of the kidney using laparoscopy. 
     
     
         24 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel that comprises constituents of extracellular matrix. 
     
     
         25 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel that comprises collagen. 
     
     
         26 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises encapsulating the plurality of islets in a hydrogel that comprises laminin. 
     
     
         27 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in a hydrogel that comprises mesenchymal stem cells. 
     
     
         28 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises providing 80,000-4,000,000 islets. 
     
     
         29 . The method according to  claim 28 , wherein providing the plurality of islets in the hydrogel comprises providing 200,000-800,000 islets. 
     
     
         30 . The method according to  claim 18 , wherein providing the plurality of islets in the hydrogel comprises providing the plurality of islets in alginate having a concentration of guluronic acid of between 30% and 50%. 
     
     
         31 . The method according to  claim 30 , wherein providing the plurality of islets in the alginate comprises providing the plurality of islets in alginate having a concentration of guluronic acid of between 40% and 47%. 
     
     
         32 . The method according to  claim 30 , wherein providing the plurality of islets in the alginate comprises providing the plurality of islets in alginate having a dry matter content of at least 1.6%. 
     
     
         33 . The method according to  claim 30 , wherein providing the plurality of islets in the alginate comprises providing the plurality of islets in alginate having a dry matter content of at least 2.1%. 
     
     
         34 . The method according to  claim 30 , wherein providing the plurality of islets in the alginate comprises providing the plurality of islets in alginate that is cross-linked with strontium. 
     
     
         35 . A method, comprising:
 providing a plurality of islets macroencapsulated in a hydro gel shaped to define a planar configuration; and   implanting the macroencapsulated islets in at least one area of a body of a subject selected from the group consisting of: a liver of the subject, an area in a vicinity of a diaphragm of the subject, and an omental pouch of the subject.   
     
     
         36 . Apparatus, comprising:
 a plurality of islets having a density of 2,000-8,000 islets/cm̂2;   an alginate structure having a planar configuration that macroencapsulates the plurality of islets, the structure configured to be implanted in a subcapsular space of a kidney of a subject, and having:
 a longest dimension between 30 mm and 120 mm, 
 a dry matter content of at least 1.6%, and 
 a concentration of guluronic acid, of between 40% and 50%. 
   
     
     
         37 . The apparatus according to  claim 36 , wherein the dry matter content of alginate in the alginate structure is between 2.1% and 5.0%. 
     
     
         38 . The apparatus according to  claim 36 , wherein the concentration of guluronic acid is between 40% and 47%. 
     
     
         39 . The apparatus according to  claim 36 , wherein the plurality of islets comprises 200,000-800,000 islets. 
     
     
         40 . A method, comprising:
 providing a plurality of islets having a density of 2,000-8,000 islets/cm̂2 macroencapsulated in an alginate structure having:
 a planar configuration, 
 a longest dimension between 30 mm and 120 mm, 
 a dry matter content of at least 1.6%, and 
 a concentration of guluronic acid of between 40% and 50%; and 
   implanting in a subcapsular space of a kidney of a subject the alginate structure that macroencapsulates the plurality of islets.   
     
     
         41 . The method according to  claim 40 , wherein providing the plurality of islets in the alginate structure comprises providing the plurality of islets in an alginate structure having a dry matter content of between 2.1% and 5.0%. 
     
     
         42 . The method according to  claim 40 , wherein providing the plurality of islets in the alginate structure comprises providing the plurality of islets in an alginate structure having a concentration of guluronic acid between 40% and 47%. 
     
     
         43 . The method according to  claim 40 , wherein providing the plurality of islets in the alginate structure comprises providing 200,000-800,000 islets.