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Engineering Protein Matrices for Production of β‐like Cells for Treatment of Type 1 Diabetes
Author(s) -
Chigumba Desnor Nicole,
Tirrell David A,
Kozlowski Mark T
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb170
Subject(s) - laminin , progenitor cell , transplantation , self healing hydrogels , cell culture , chemistry , progenitor , sequence (biology) , cell , computational biology , microbiology and biotechnology , biochemistry , stem cell , biology , medicine , genetics , organic chemistry
Type 1 diabetes is a chronic condition in which patients cannot produce their own insulin. Previous studies have shown that it is possible to manipulate post‐natal progenitor cells to differentiate directly into β‐cells for transplantation by using laminin and methylcellulose to provide the appropriate biochemical and mechanical cues respectively. By using engineered protein hydrogels with an encoded laminin sequence and leucine zippers, we can make a material that provides both cues. As the cell culture is 3‐dimensional, this would enable us to suspend the cells in solution. Our primary objective was to produce a hydrogel which would be soluble at 37°C. Previous protein constructs were not soluble and we suspect this was because they had low LCSTs. Therefore, we altered the sequence to increase solubility. We cloned a PC 10 ‐lam‐C 10 P protein where the C domain is hydrophilic and does not have an LCST. PE 6 ‐lam‐E 6 P, PE 6 ‐trunc lam‐E 6 P and PE 6 ‐lam‐E 6 P C3A were also constructed as modifications of a previous elastin PEP construct. All constructs were soluble and MALDI‐TOF MS suggests we obtained our protein of interest. All constructs are sent to City of Hope Hospital for cell culture studies. Support or Funding Information California Institute of Technology SURF program