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Remote control of the recruitment and capture of endogenous stem cells by ultrasound for in situ repair of bone defects

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Bioactive Materials 2023年第3期21卷 223-238页

作者： Yanni He Fei Li Peng Jiang Feiyan Cai Qin Lin Meijun Zhou Hongmei Liu Fei Yan Department of Ultrasound Institute of Ultrasound in Musculoskeletal Sports MedicineGuangdong Second Provincial General HospitalGuangzhou510317PR China The Second School of Clinical Medicine Southern Medical UniversityGuangzhou510515China Paul C.Lauterbur Research Center for Biomedical Imaging Institute of Biomedical and Health EngineeringShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen518055People’s Republic of China Center for Cell and Gene Circuit Design CAS Key Laboratory of Quantitative Engineering BiologyShenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen518055People’s Republic of China

stem cell-based tissue engineering has provided a promising platform for repairing of bone ***,the use of exogenous bone marrow mesenchymal stem cells(BMSCs)still faces many challenges such as limited sources and potential *** is important to develop new approach to effectively recruit endogenous BMSCs and capture them for in situ bone ***,we designed an acoustically responsive scaffold(ARS)and embedded it into SDF-1/BMP-2 loaded hydrogel to obtain biomimetic hydrogel scaffold complexes(BSC).The SDF-1/BMP-2 cytokines can be released on demand from the BSC implanted into the defected bone via pulsed ultrasound(p-US)irradiation at optimized acoustic parameters,recruiting the endogenous BMSCs to the bone defected or BSC *** by the daily p-US irradiation for 14 days,the alginate hydrogel was degraded,resulting in the exposure of ARS to these recruited host stem *** another set of sinusoidal continuous wave ultrasound(s-US)irradiation was applied to excite the ARS intrinsic resonance,forming highly localized acoustic field around its surface and generating enhanced acoustic trapping force,by which these recruited endogenous stem cells would be captured on the scaffold,greatly promoting them to adhesively grow for in situ bone tissue *** study provides a novel and effective strategy for in situ bone defect repairing through acoustically manipulating endogenous BMSCs.

关键词： Acoustically responsive scaffolds Biomimetic hydrogel scaffold complexes endogenous stem cells Acoustic radiation force Bone defect repairing

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A bioactive material with dual integrin-targeting ligands regulates specific endogenous cell adhesion and promotes vascularized bone regeneration in adult and fetal bone defects

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Bioactive Materials 2023年第2期20卷 179-193页

作者： Dake Hao Ruiwu Liu Tomas Gonzalez Fernandez Christopher Pivetti Jordan Elizabeth Jackson Edwin Samuel Kulubya Hong-Jiang Jiang Hai-Yang Ju Wen-Liang Liu Alyssa Panitch Kit S.Lam JKent Leach Diana L.Farmer Aijun Wang Department of Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States Institute for Pediatric Regenerative Medicine Shriners Hospitals for ChildrenSacramentoCA95817United States Department of Biochemistry and Molecular Medicine School of MedicineUniversity of California DavisSacramentoCA95817United States Department of Biomedical Engineering University of California DavisDavisCA95616United States Wendeng Orthopaedic Hospital No.1 Fengshan RoadWendeng264400ShandongChina Department of Orthopaedic Surgery School of MedicineUniversity of California DavisSacramentoCA95817United States

Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone ***,current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration,thus leading to adverse tissue formation and decreased regenerative ***,we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone *** biomaterial works by presenting two synthetic ligands,LLP2A and LXW7,explicitly targeting integrinsα4β1 andαvβ3,respectively,expressed on the surfaces of the cells related to bone formation and vascularization,such as mesenchymal stem cells(MSCs),osteoblasts,endothelial progenitor cells(EPCs),and endothelial cells(ECs).In vitro,the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs,osteoblasts,EPCs,and ECs via integrinα4β1 andαvβ3,*** an adult rat calvarial bone defect model,the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials,such as DLX5^(+)cells,osteocalcin^(+)cells,CD34^(+)/CD45-cells and CD31^(+)*** a fetal sheep spinal bone defect model,the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse *** innovative biomaterial offers an off-the-shelf,easy-to-use,and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.

关键词： Integrin-based ligands endogenous stem cells Bone formation Vascularization Adult and fetal bone defects

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Priming of the cells： Hypoxic Preconditioning for stem Cell Therapy

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Chinese Medical Journal 2017年第19期130卷 2361-2374页

作者： Zheng Z Wei Yan-Bing Zhu James Y Zhang Myles R McCrary Song Wang Yong-Bo Zhang Shan-Ping Yu Ling Wei Department of Neurology Beijing Friendship Hospital Capital Medical University Beijing 100050 China Experimental and Translational Research Center Beijing Friendship Hospital Capital Medical University Beijing 100050 China Department of Anesthesiology Emory University School of Medicine Atlanta Georgia 30322 USA

Objective： stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. Data Sources： This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords：＂stem cells,＂＂hypoxic preconditioning,＂＂ischemic preconditioning,＂ and ＂cell transplantation.＂Study Selection： Original articles and critical reviews on the topics were selected. Results： Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. Conclusions： In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applicatio

关键词： Angiogenesis Factor Cell Transplantation endogenous stem cells Genome Editing Hypoxia Hypoxic Preconditioning Induced Pluripotent stem cells Neurological Disorders Tumor

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EndoN treatment allows neuroblasts to leave the rostral migratory stream and migrate towards a lesion within the prefrontal cortex of rats

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Neural Regeneration Research 2020年第9期15卷 1740-1747页

作者： Jannis Gundelach Michael Koch Department of Neuropharmacology Center for Cognitive Sciences University of Bremen

The binding properties of neural cell adhesion molecule are modulated by a polysialic acid moiety. This plays an important role in the migration of adult born neuroblasts from their area of origin, the subventricular zone, towards the olfactory bulb. Polysialisation increases the migration speed of the cells and helps to prevent the neuroblasts from leaving their migration route, the rostral migratory stream. Here, we evaluated the potential of intraventricular application of endoneuraminidase-N, an enzyme that specifically cleaves polysialic acid from neural cell adhesion molecule, in a rat model for structural prefrontal cortex damage. As expected, endoneuraminidase-N caused the rostral migratory stream to become wider, with a less uniform cellular orientation. Furthermore, endoneuraminidase-N treatment caused the neuroblasts to leave the rostral migratory stream and migrate towards the lesioned tissue. Despite the neuroblasts not being differentiated into neurons after a survival time of three weeks, this technique provides a solid animal model for future work on the migration and differentiation of relocated neuroblasts and might provide a basis for a future endogenous stem cell-based therapy for structural brain damage. The experiments were approved by the local animal care committee(522-27-11/02-00, 115;Senatorin für Wissenschaft, Gesundheit und Verbraucherschutz, Bremen, Germany) on February 10, 2016.

关键词： endogenous stem cells endoneuraminidase neural cell adhesion molecule neuroblast migration olfactory bulb polisialic acid structural brain damage subventricular zone

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Dl-3-butylphthalide-enhanced hematopoietic stem cell transplantation and endogenous stem cell mobilization for the treatment of cerebral infarcts

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Neural Regeneration Research 2011年第7期6卷 494-499页

作者： Baoquan Lu Xiaoming Shang Yongqiu Li Hongying Ma Chunqin Liu Jianmin Li Yingqi Zhang Shaoxin Yao Department of Neurology Tangshan Workers' Hospital Hebei Medical University Tangshan 063000 Hebei Province China Department of Cardiology Tangshan Workers' Hospital Hebei Medical University Tangshan 063000 Hebei Province China Department of Neurosurgery Affiliated Hospital of Hebei United University Tangshan 063000 Hebei Province China Department of Infectious Diseases Tangshan Workers' Hospital Hebei Medical University Tangshan 063000 Hebei Province China Department of Radiology Tangshan Workers' Hospital Hebei Medical University Tangshan 063000 Hebei Province China

Exogenous stem cell transplantation and endogenous stem cell mobilization are both effective for the treatment of acute cerebral infarction. The compound dl-3-butylphthalide is known to improve microcirculation and help brain cells at the infarct loci. This experiment aimed to investigate the effects of dl-3-butylphthalide intervention based on the transplantation of hematopoietic stem cells and mobilization of endogenous stem cells in a rat model of cerebral infarction, following middle cerebral artery occlusion. Results showed that neurological function was greatly improved and infarct volume was reduced in rats with cerebral infarction. Data also showed that dl-3-butylphthalide can promote hematopoietic stem cells to transform into vascular endothelial cells and neuronal-like cells, and also enhance the therapeutic effect on cerebral infarction by hematopoietic stem cell transplantation and endogenous stem cell mobilization.

关键词： dl-3-butylphthalide hematopoietic stem cells endogenous stem cells infarction stem cell mobilization neural regeneration

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Current evidence on potential of adipose derived stem cells to enhance bone regeneration and future projection

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World Journal of stem cells 2021年第9期13卷 1248-1277页

作者： Quang Le Vedavathi Madhu Joseph M Hart Charles R Farber Eli R Zunder Abhijit S Dighe Quanjun Cui Department of Orthopaedic Surgery University of Virginia School of MedicineCharlottesvilleVA 22908United States Orthopaedic Surgery Research Thomas Jefferson UniversityPhiladelphiaPA 19107United States Center for Public Health Genomics University of VirginiaCharlottesvilleVA 22908United States Departments of Public Health Sciences and Biochemistry and Molecular Genetics University of VirginiaCharlottesvilleVA 22908United States Department of Biomedical Engineering University of VirginiaCharlottesvilleVA 22908United States

Injuries to the postnatal skeleton are naturally repaired through successive stepsinvolving specific cell types in a process collectively termed “bone regeneration”.Although complex, bone regeneration occurs through a series of well-orchestratedstages wherein endogenous bone stem cells play a central role. In most situations,bone regeneration is successful;however, there are instances when it fails andcreates non-healing injuries or fracture nonunion requiring surgical or therapeuticinterventions. Transplantation of adult or mesenchymal stem cells (MSCs) definedby the International Society for Cell and Gene Therapy (ISCT) as CD105+-CD90+CD73+CD45-CD34-CD14orCD11b-CD79αorCD19-HLA-DR- is beinginvestigated as an attractive therapy for bone regeneration throughout the *** isolated from adipose tissue, adipose-derived stem cells (ADSCs), aregaining increasing attention since this is the most abundant source of adult stemcells and the isolation process for ADSCs is straightforward. Currently, there isnot a single Food and Drug Administration (FDA) approved ADSCs product forbone regeneration. Although the safety of ADSCs is established from their usagein numerous clinical trials, the bone-forming potential of ADSCs and MSCs, ingeneral, is highly controversial. Growing evidence suggests that the ISCT definedphenotype may not represent bona fide osteoprogenitors. Transplantation of bothADSCs and the CD105- sub-population of ADSCs has been reported to induce bone regeneration. Most notably, cells expressing other markers such as CD146,AlphaV, CD200, PDPN, CD164, CXCR4, and PDGFRα have been shown torepresent osteogenic sub-population within ADSCs. Amongst other strategies toimprove the bone-forming ability of ADSCs, modulation of VEGF, TGF-β1 andBMP signaling pathways of ADSCs has shown promising results. The U.S. FDAreveals that 73% of Investigational New Drug applications for stem cell-basedproducts rely on CD105 expression as the “positive” marker for adult stem cell

关键词： Mesenchymal stem cells Adipose-derived stem cells endogenous stem cells Skeletal stem cells Bone regeneration

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