Journal
EJNMMI RESEARCH
Volume 4, Issue -, Pages 1-11Publisher
SPRINGEROPEN
DOI: 10.1186/s13550-014-0061-3
Keywords
Gelatin-based hydrogel; Matrix elasticity; Human neural stem cell; In vivo bioluminescence imaging; Optical kinetics
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2012R1A1A2008799]
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [HI13C1299]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C1277]
- National Research Foundation of Korea [2012R1A1A2008799] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Background: Three-dimensional (3D) hydrogel-based stem cell therapies contribute to enhanced therapeutic efficacy in treating diseases, and determining the optimal mechanical strength of the hydrogel in vivo is important for therapeutic success. We evaluated the proliferation of human neural stem cells incorporated within in situ-forming hydrogels and compared the effect of hydrogels with different elastic properties in cell/hydrogel-xenografted mice. Methods: The gelatin-polyethylene glycol-tyramine (GPT) hydrogel was fabricated through enzyme-mediated cross-linking reaction using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). Results: The F3-effluc encapsulated within a soft 1,800 pascal (Pa) hydrogel and stiff 5,800 Pa hydrogel proliferated vigorously in a 24-well plate until day 8. In vitro and in vivo kinetics of luciferase activity showed a slow time-to-peak after D-luciferin administration in the stiff hydrogel. When in vivo proliferation of F3-effluc was observed up to day 21 in both the hydrogel group and cell-only group, F3-effluc within the soft hydrogel proliferated more vigorously, compared to the cells within the stiff hydrogel. Ki-67-specific immunostaining revealed highly proliferative F3-effluc with compactly distributed cell population inside the 1,800 Pa or 5,800 Pa hydrogel. Conclusions: We examined the in vivo effectiveness of different elastic types of hydrogels encapsulating viable neural stem cells by successfully monitoring the proliferation of implanted stem cells incorporated within a 3D hydrogel scaffold.
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