title: The generation of hybrid electrospun nanofiber layer with extracellular matrix derived from human pluripotent stem cells, for regenerative medicine applications.
abstract: Extracellular matrix (ECM) has been utilized as a biological scaffold for tissue engineering applications in a variety of body systems, due to its bioactivity and biocompatibility. In the current study we developed a modified protocol for the efficient and reproducible derivation of mesenchymal progenitor cells (MPCs) from human embryonic stem cells as well as human induced pluripotent stem cells (hiPSCs) originating from hair follicle keratinocytes (HFKTs). ECM was produced from these MPCs and characterized in comparison to adipose mesenchymal stem cell ECM, demonstrating robust ECM generation by the excised HFKT-iPSC-MPCs. Exploiting the advantages of electrospinning we generated two types of electrospun biodegradable nanofiber layers (NFLs), fabricated from polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA), which provide mechanical support for cell seeding and ECM generation. Elucidating the optimized decellularization treatment we were able to generate an available "off-the-shelf" implantable product (NFL-ECM). Using rat subcutaneous transplantation model we demonstrate that this stem-cell-derived construct is biocompatible and biodegradable and holds great potential for tissue regeneration applications.
authors.affiliation: 1 The Berlin Family Laboratory for Stem Cell Research, The Sohnis and Forman Families Stem Cell Center for Stem Cell and Tissue Regeneration Research, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology , Haifa, Israel .
authors.forename: Ronit
authors.initials: R
authors.lastname: Shtrichman
authors.forename: Naama
authors.initials: N
authors.lastname: Zeevi-Levin
authors.forename: Rinat
authors.initials: R
authors.lastname: Zaid
authors.forename: Efrat
authors.initials: E
authors.lastname: Barak
authors.forename: Bettina
authors.initials: B
authors.lastname: Fishman
authors.forename: Anna
authors.initials: A
authors.lastname: Ziskind
authors.forename: Rita
authors.initials: R
authors.lastname: Shulman
authors.forename: Atara
authors.initials: A
authors.lastname: Novak
authors.forename: Ron
authors.initials: R
authors.lastname: Avrahami
authors.forename: Erella
authors.initials: E
authors.lastname: Livne
authors.forename: Lior
authors.initials: L
authors.lastname: Lowenstein
authors.forename: Eyal
authors.initials: E
authors.lastname: Zussman
authors.forename: Joseph
authors.initials: J
authors.lastname: Itskovitz-Eldor
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry*; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D057139:Nanofibers / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D044968:Regenerative Medicine
chemical_list: D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid