Tissue-engineered fibrin scaffolds containing neural progenitors enhance functional recovery in a subacute model of SCI.
Tissue-engineered fibrin scaffolds containing neural progenitors enhance functional recovery in a subacute model of SCI.
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DOI：
10.1039/c0sm00173b
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发表时间：
2010-10-21
期刊：
影响因子：
3.4
通讯作者：
Sakiyama-Elbert SE
中科院分区：
文献类型：
--
作者：
Johnson PJ;Tatara A;McCreedy DA;Shiu A;Sakiyama-Elbert SE
干细胞/神经祖细胞（NPC）移植治疗脊髓损伤（SCI）的两个反复出现的问题是细胞存活率差和细胞分化失控。目前的研究评估了胚胎干细胞衍生的神经祖细胞（ESNPCs）在含有生长因子（GFs）和肝素结合递送系统（HBDS）的纤维蛋白支架内移植的活力和分化，以增强细胞存活和直接分化为神经元。使用4−/4+维甲酸（RA）诱导方案，从小鼠胚胎干细胞（ESCs）中生成小鼠esnpc，导致70%的巢素阳性NPCs细胞群体。将ESNPCs直接移植到大鼠亚急性背半球损伤模型中。ESNPCs被包裹在纤维蛋白支架中；包裹在含有HBDS、神经营养因子-3 （NT-3）和血小板衍生生长因子（PDGF-AA）的纤维蛋白中；或者用NT-3和PDGF-AA包封在纤维蛋白支架中，没有HBDS。我们报道了GFs和纤维蛋白支架（不含HBDS）的联合使用增加了治疗脊髓中esnpc的总数，并在移植后8周增加了esnpc衍生的NeuN阳性神经元的数量。用ESNPCs处理的所有实验组在移植后4周均表现出行为功能的增加。在一部分动物中，4周和8周时发现的SSEA-1阳性/Ki67阳性espcs证明了esnpc过度增殖。这些结果证明了组织工程纤维蛋白支架在提高npc存活率方面的潜力，并强调了纯化脊髓损伤治疗中使用的细胞群的必要性。
Two recurring problems with stem/neural progenitor cell (NPC) transplantation therapies for spinal cord injury (SCI) are poor cell survival and uncontrolled cell differentiation. The current study evaluated the viability and differentiation of embryonic stem cell-derived neural progenitor cells (ESNPCs) transplanted within fibrin scaffolds containing growth factors (GFs) and a heparin-binding delivery system (HBDS) to enhance cell survival and direct differentiation into neurons. Mouse ESNPCs were generated from mouse embryonic stem cells (ESCs) using a 4−/4+ retinoic acid (RA) induction protocol that resulted in a population of cells that was 70% nestin positive NPCs. The ESNPCs were transplanted directly into a rat subacute dorsal hemisection lesion SCI model. ESNPCs were either encapsulated in a fibrin scaffold; encapsulated in fibrin containing the HBDS, neurotrophin-3 (NT-3) and platelet derived growth factor (PDGF-AA); or encapsulated in fibrin scaffolds with NT-3 and PDGF-AA without the HBDS. We report that the combination of GFs and fibrin scaffold (without HBDS) enhanced the total number of ESNPCs present in the treated spinal cords and increased the number of ESNPC-derived NeuN positive neurons 8 weeks after transplantation. All experimental groups treated with ESNPCs exhibited an increase in behavioral function 4 weeks after transplantation. In a subset of animals, the ESNPCs over-proliferated as evidenced by SSEA-1 positive/Ki67 positive ESCs found at 4 and 8 weeks. These results demonstrate the potential of tissue-engineered fibrin scaffolds to enhance the survival of NPCs and highlight the need to purify cell populations used in therapies for SCI.
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影响因子：
14
作者：
Willerth, Stephanie M.;Arendas, Kelly J.;Sakiyama-Elbert, Shelly Elese
通讯作者：
Sakiyama-Elbert, Shelly Elese
影响因子：
82.9
作者：
Eriksson, PS;Perfilieva, E;Gage, FH
通讯作者：
Gage, FH
影响因子：
4.8
作者：
Nussbaum, Jeannette;Minami, Elina;Murry, Charles E.
通讯作者：
Murry, Charles E.
影响因子：
6.2
作者：
Fressinaud, C
通讯作者：
Fressinaud, C
影响因子：
2.4
作者：
McMahon, Siobhan S.;Albermann, Silke;Barry, Frank P.
通讯作者：
Barry, Frank P.