Lee Young Sook, Lim Kwang Suk, Oh Jung-Eun, Yoon A-Rum, Joo Wan Seok, Kim Hyun Soo, Yun Chae-Ok, Kim Sung Wan
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.
J Control Release. 2015 May 10;205:128-33. doi: 10.1016/j.jconrel.2015.01.004. Epub 2015 Jan 7.
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.
多能间充质干细胞（MSCs）有望为许多使人衰弱且无法治愈的疾病提供一种治疗选择。然而，人类间充质干细胞（hMSC）治疗应用的主要限制之一是由于移植后植入率低，需要较长的体外扩增时间来制备足够数量的细胞。为了解决这一难题，研究了一种多孔可生物降解聚合物微球作为递送MSCs的潜在支架。采用改进的水/油/水（W1/O/W2）双乳液溶剂蒸发法构建多孔微球。将PEI1.8k与聚乳酸-乙醇酸共聚物（PLGA）混合，以增强细胞与微球的静电附着。多孔PLGA/PEI1.8k（PPP）颗粒的平均粒径为290μm，平均孔径为14.3μm，为MSCs递送提供了一种微载体。与无孔PLGA/PEI1.8k（NPP）颗粒、无孔（NP）和多孔PLGA（PP）微球相比，PPP颗粒能使大鼠骨髓间充质干细胞（rMSCs）更好地附着。rMSC在PPP颗粒上成功体外生长2周。接下来，与心肌内给药2周后的单纯hMSC组相比，负载3种不同数量hMSC的PPP颗粒在体内的植入率增加，并保持了hMSC的干性特征。这些用于MSC递送的定制PPP颗粒是一种可生物降解且可注射的支架，可用于临床应用。
