title: Development of porous PLGA/PEI1.8k biodegradable microspheres for the delivery of mesenchymal stem cells (MSCs).
abstract: Multipotent mesenchymal stem cells (MSCs) promise a therapeutic alternative for many debilitating and incurable diseases. However, one of the major limitations for the therapeutic application of human MSC (hMSC) is the lengthy ex vivo expansion time for preparing a sufficient amount of cells due to the low engraftment rate after transplantation. To solve this conundrum, a porous biodegradable polymeric microsphere was investigated as a potential scaffold for the delivery of MSCs. The modified water/oil/water (W1/O/W2) double emulsion solvent evaporation method was used for the construction of porous microspheres. PEI1.8k was blended with poly(lactic-co-glycolic acid) (PLGA) to enhance electrostatic cellular attachment to the microspheres. The porous PLGA/PEI1.8k (PPP) particles demonstrated an average particle size of 290μm and an average pore size of 14.3μm, providing a micro-carrier for the MSC delivery. PPP particles allowed for better attachment of rMSCs than non-porous PLGA/PEI1.8k (NPP) particles and non-porous (NP) and porous PLGA (PP) microspheres. rMSC successfully grew on the PPP particles for 2weeks in vitro. Next, PPP particles loaded with 3 different amounts of hMSC showed increased in vivo engraftment rates and maintained the stemness characteristics of hMSC compared with hMSCs-alone group in rats 2weeks after intramyocardial administration. These customized PPP particles for MSC delivery are a biodegradable and injectable scaffold that can be used for clinical applications.
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA.
authors.forename: Young Sook
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA.
authors.forename: Kwang Suk
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Oh
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: A-Rum
authors.initials: AR
authors.lastname: Yoon
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Wan Seok
authors.initials: WS
authors.lastname: Joo
authors.affiliation: Pharmicell Co., Ltd., Sungnam, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; Department of Bioengineering, Hanyang University, Seoul, Republic of Korea. Electronic address: sw.kim@pharm.utah.edu.
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006085:Graft Survival; D006801:Humans; D007097:Imines / Q000737:chemistry*; D015552:Injections, Intralesional; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008863:Microspheres; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D010316:Particle Size; D011095:Polyethylenes / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013997:Time Factors; D054457:Tissue Scaffolds
chemical_list: D007097:Imines; D011095:Polyethylenes; C505405:poly(ethylene imine); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Cell therapy; Human stem cell; Mesenchymal stem cell; PEI(1.8k); PLGA; Porous microparticle