title: Inkjet printing of macromolecules on hydrogels to steer neural stem cell differentiation.
abstract: Inkjet printing allows for the rapid and inexpensive printing of cells, materials, and protein molecules. However, the combination of inkjet printing and control of neural stem cell (NSC) multipotency and differentiation has remained unexplored. We used an inkjet printer (Canon BJC-2100) to print biologically active macromolecules on poly-acrylamide-based hydrogels (HydroGel(TM)), which were subsequently seeded with primary fetal NSCs. NSCs cultured on areas printed with fibroblast growth factor-2 (FGF2) remained undifferentiated, consistent with the effects of FGF2 when administered in solution. NSCs cultured in parallel on the same hydrogels but in areas printed with ciliary neurotrophic factor (CNTF) or fetal bovine serum (FBS) displayed a rapid induction of markers for astrocytic (glial fibrillary acidic protein, GFAP) or smooth muscle (smooth muscle actin, SMA) differentiation, respectively. These results are consistent with known actions of CNTF and FBS on NSCs. Importantly, NSCs cultured on a printed gradient of increasing levels of CNTF showed a linear increase in numbers of cells expressing GFAP, demonstrating a functional gradient of CNTF. Lastly, genetically modified NSCs proved to respond properly to printed macromolecules, suggesting that inkjet printing can successfully be combined with gene delivery to achieve effective control of stem cell differentiation.
authors.affiliation: Center of Excellence in Developmental Biology (CEDB/DBRM), Organic Bioelectronics (OBOE), Department of Neuroscience, Karolinska Institutet, SE17177 Stockholm, Sweden.
authors.forename: Shirin
authors.initials: S
authors.lastname: Ilkhanizadeh
authors.forename: Ana I
authors.initials: AI
authors.lastname: Teixeira
authors.forename: Ola
authors.initials: O
authors.lastname: Hermanson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016287:Computer Peripherals; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011327:Printing / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D046911:Macromolecular Substances