Gelatinized copper-capillary alginate gel functions as an injectable tissue scaffolding system for stem cell transplants.
In severe hypoxic-ischemic brain injury, cellular components such as neurons and astrocytes are injured or destroyed along with the supporting extracellular matrix. This presents a challenge to the field of regenerative medicine since the lack of extracellular matrix and supporting structures makes the transplant milieu inhospitable to the transplanted cells. A potential solution to this problem is the use of a biomaterial to provide the extracellular components needed to keep cells localized in cystic brain regions, allowing the cells to form connections and repair lost brain tissue. Ideally, this biomaterial would be combined with stem cells, which have been proven to have therapeutic potentials, and could be delivered via an injection. To study this approach, we derived a hydrogel biomaterial tissue scaffold from oligomeric gelatin and copper-capillary alginate gel (GCCAG). We then demonstrated that our multipotent astrocytic stem cells (MASCs) could be maintained in GCCAG scaffolds for up to 2 weeks in vitro and that the cells retained their multipotency. We next performed a pilot transplant study in which GCCAG was mixed with MASCs and injected into the brain of a neonatal rat pup. After a week in vivo, our results showed that: the GCCAG biomaterial did not cause a significant reactive gliosis; viable cells were retained within the injected scaffolds; and some delivered cells migrated into the surrounding brain tissue. Therefore, GCCAG tissue scaffolds are a promising, novel injectable system for transplantation of stem cells to the brain.
Willenberg
Bradley Jay
BJ
Department of Materials Science and Engineering, University of Florida, Gainesville, 32611-6400, USA. yoda@ufl.edu
Zheng
Tong
T
Meng
Fan-Wei
FW
Meneses
Juan Carlos
JC
Rossignol
Candace
C
Batich
Christopher D
CD
Terada
Naohiro
N
Steindler
Dennis A
DA
Weiss
Michael D
MD
D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D005780:Gelatin / Q000737:chemistry*; D005782:Gels; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007267:Injections; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000637:transplantation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*
D000464:Alginates; D005782:Gels; D006603:Hexuronic Acids; D003300:Copper; D020723:Glucuronic Acid; D005780:Gelatin