PMID- 27592818 OWN - NLM STAT- MEDLINE DCOM- 20171030 LR - 20181202 IS - 1878-7568 (Electronic) IS - 1742-7061 (Linking) VI - 45 DP - 2016 Nov TI - Transplantation of RADA16-BDNF peptide scaffold with human umbilical cord mesenchymal stem cells forced with CXCR4 and activated astrocytes for repair of traumatic brain injury. PG - 247-261 LID - S1742-7061(16)30464-0 [pii] LID - 10.1016/j.actbio.2016.09.001 [doi] AB - Due to the poor self-regeneration of brain tissue, stem cell transplantation therapy is purported to enable the replacement of lost neurons after traumatic brain injury (TBI). The main challenge of brain regeneration is whether the transplanted cells can survive and carry out neuronal functions in the lesion area. The brain is a complex neuronal network consisting of various types of cells that significantly influence on each other, and the survival of the implanted stem cells in brain is critically influenced by the surrounding cells. Although stem cell-based therapy is developing rapidly, most previous studies just focus on apply single type of stem cells as cell source. Here, we found that co-culturing human umbilical cord mesenchymal stem cells (hUC-MSCs) directly with the activated astrocytes benefited to the proliferation and neuron differentiation of hUC-MSCs in vitro. In this study, hUC-MSCs and the activated astrocytes were seeded in RADA16-BDNF peptide scaffold (R-B-SPH scaffold), a specifical self-assembling peptide hydrogel, in which the environment promoted the differentiation of typical neuron-like cells with neurites extending in three-dimensional directions. Moreover, the results showed co-culture of hUC-MSCs and activated astrocytes promoted more BDNF secretion which may benefit to both neural differentiation of ectogenic hUC-MSCs and endogenic neurogenesis. In order to promote migration of the transplanted hUC-MSCs to the host brain, the hUC-MSCs were forced with CXC chemokine receptor 4 (CXCR4). We found that the moderate-sized lesion cavity, but not the large cavity caused by TBI was repaired via the transplantation of hUC-MSCs(CXCR4) and activated astrocytes embedded in R-B-SPH scaffolds. The functional neural repair for TBI demonstrated in this study is mainly due to the transplantation system of double cells, hUC-MSCs and activated astrocytes. We believe that this novel cell transplantation system offers a promising treatment option for cell replacement therapy for TBI. STATEMENT OF SIGNIFICANCE: In this reach, we specifically linked RGIDKRHWNSQ, a functional peptide derived from BDNF, to the C-terminal of RADARADARADARADA (RADA16) to structure a functional self-assembling peptide hydrogel scaffold, RADA16-BDNF (R-B-SPH scaffold) for the better transplantation of the double cell unit. Also, the novel scaffold was used as cell-carrier for transplantation double cell unit (hUC-MSCs/astrocyte) for treating traumatic brain injury. The results of this study showing that R-B-SPH scaffold was pliancy and flexibility to fit the brain lesion cavity and promotes the outgrowth of axons and dendrites of the neurons derived from hUC-MSCs in vitro and in vivo, indicating the 3D R-B-SPH scaffold provided a suitable microenvironment for hUC-MSC survival, proliferation and differentiation. Also, our results showing the double-cells transplantation system (hUC-MSCs/astrocyte) may be a novel cell-based therapeutic strategy for neuroregeneration after TBI with potential value for clinical application. CI - Copyright (c) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. FAU - Shi, W AU - Shi W AD - Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China; Department of Neurosurgery, Xinhua Hospital of Kazak Autonomous Prefecture of Ili, Sinkiang 835000, China; Department of Laboratory of Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Huang, C J AU - Huang CJ AD - Department of Neurosurgery, The First People's Hospital of Wujiang, Soochow 215200, China; Department of Laboratory of Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Xu, X D AU - Xu XD AD - Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Jin, G H AU - Jin GH AD - Department of Anatomy and Neurobiology, School of Medicine, Nantong University, Nantong 226001, China. FAU - Huang, R Q AU - Huang RQ AD - Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China. FAU - Huang, J F AU - Huang JF AD - Department of Pathology and Clinical Biobank, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Chen, Y N AU - Chen YN AD - Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Ju, S Q AU - Ju SQ AD - Department of Laboratory of Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Wang, Y AU - Wang Y AD - Center of Analysis and Measurement, Fudan University, Shanghai 200433, China. FAU - Shi, Y W AU - Shi YW AD - Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China. FAU - Qin, J B AU - Qin JB AD - Department of Anatomy and Neurobiology, School of Medicine, Nantong University, Nantong 226001, China. FAU - Zhang, Y Q AU - Zhang YQ AD - Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Liu, Q Q AU - Liu QQ AD - Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Wang, X B AU - Wang XB AD - Medical Image Center, Affiliated Hospital of Nantong University, Nantong 226001, China. FAU - Zhang, X H AU - Zhang XH AD - Department of Anatomy and Neurobiology, School of Medicine, Nantong University, Nantong 226001, China. Electronic address: zhangxinhua@ntu.edu.cn. FAU - Chen, J AU - Chen J AD - Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong 226001, China. Electronic address: ntfychenjian@126.com. LA - eng PT - Journal Article DEP - 20160902 PL - England TA - Acta Biomater JT - Acta biomaterialia JID - 101233144 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Chemokine CXCL12) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Peptides) RN - 0 (RADA16-I) RN - 0 (Receptors, CXCR4) SB - IM MH - Animals MH - Astrocytes/drug effects/*metabolism MH - Brain Injuries, Traumatic/pathology/*therapy MH - Brain-Derived Neurotrophic Factor/pharmacology/*therapeutic use MH - Cell Adhesion/drug effects MH - Cell Differentiation/drug effects MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Chemokine CXCL12/metabolism MH - Coculture Techniques MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - Magnetic Resonance Imaging MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology/drug effects MH - Neural Stem Cells/cytology/drug effects MH - Neurons/drug effects/pathology MH - Peptides/pharmacology/*therapeutic use MH - Rats, Sprague-Dawley MH - Receptors, CXCR4/*metabolism MH - Regeneration/drug effects MH - Synapses/drug effects/metabolism MH - Tissue Scaffolds/*chemistry MH - Umbilical Cord/cytology OTO - NOTNLM OT - Astrocytes OT - CXCR4/SDF-1axis OT - Neuronal differentiation OT - Peptide hydrogel OT - Transplantation OT - Traumatic brain injury OT - hUC-MSCs EDAT- 2016/10/19 06:00 MHDA- 2017/10/31 06:00 CRDT- 2016/09/06 06:00 PHST- 2016/05/11 00:00 [received] PHST- 2016/08/19 00:00 [revised] PHST- 2016/09/01 00:00 [accepted] PHST- 2016/10/19 06:00 [pubmed] PHST- 2017/10/31 06:00 [medline] PHST- 2016/09/06 06:00 [entrez] AID - S1742-7061(16)30464-0 [pii] AID - 10.1016/j.actbio.2016.09.001 [doi] PST - ppublish SO - Acta Biomater. 2016 Nov;45:247-261. doi: 10.1016/j.actbio.2016.09.001. Epub 2016 Sep 2.