Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain

Autor: Jessica K Cinkornpumin, Tatiana Segura, S. Thomas Carmichael, William E. Lowry, Irene L. Llorente, Lina R. Nih, Pouria Moshayedi, Andrew R. Berg
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
medicine.medical_treatment
Cellular differentiation
Inbred C57BL
Regenerative Medicine
Mice
Neural Stem Cells
Stem Cell Research - Nonembryonic - Human
Materials Testing
Hyaluronic Acid
Hyaluronan
Cells
Cultured
Cultured
Tissue Scaffolds
Chemistry
Viscosity
iPS
Brain
Cell Differentiation
Hydrogels
Stem-cell therapy
Neural stem cell
Cell biology
Stroke
Treatment Outcome
Mechanics of Materials
Neurological
Self-healing hydrogels
Stem Cell Research - Nonembryonic - Non-Human
Development of treatments and therapeutic interventions
Stem cell
Astrocyte
Cell Survival
Surface Properties
Cells
1.1 Normal biological development and functioning
Biomedical Engineering
Biophysics
Bioengineering
Cell fate determination
Article
Biomaterials
03 medical and health sciences
Underpinning research
Tensile Strength
medicine
Regeneration
Animals
Humans
Stem Cell Research - Embryonic - Human
Transplantation
5.2 Cellular and gene therapies
Guided Tissue Regeneration
Regeneration (biology)
Neurosciences
technology
industry
and agriculture
Stem Cell Research
Brain Disorders
Mice
Inbred C57BL
030104 developmental biology
Ceramics and Composites
Angiogenesis
Biomedical engineering
Stem Cell Transplantation
Zdroj: Moshayedi, P; Nih, LR; Llorente, IL; Berg, AR; Cinkornpumin, J; Lowry, WE; et al.(2016). Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain. BIOMATERIALS, 105, 145-155. doi: 10.1016/j.biomaterials.2016.07.028. UCLA: Retrieved from: http://www.escholarship.org/uc/item/9t02j558
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2016.07.028
Popis: Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold. First, we optimized stiffness for a minimal reaction of adjacent brain to the transplant. Next hydrogel crosslinkers sensitive to matrix metalloproteinases (MMP) were incorporated as they promoted vascularization. Finally, candidate adhesion motifs and growth factors were systemically changed invitro using a design of experiment approach to optimize stem cell survival or proliferation. The optimized HA hydrogel, tested invivo, promoted survival of encapsulated human neural progenitor cells (iPS-NPCs) after transplantation into the stroke core and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. This HA hydrogel can be tracked invivo with MRI. A hydrogel can serve as a therapeutic adjunct in a stem cell therapy through selective control of stem cell survival and differentiation invivo.
Databáze: OpenAIRE
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