Mesenchymal Stem Cell Homing: The Devil Is in the Details

Karp, Jeffrey M.; Teo, Grace Sock Leng

doi:10.1016/j.stem.2009.02.001

Cited by 1,271 publications

(1,155 citation statements)

References 97 publications

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“…Exogenous undifferentiated MSCs such as those used by us have more homing and differentiation abilities than differentiated MSCs. 19,20 The more differentiated …”

Section: Discussionmentioning

confidence: 99%

Tissue engineering‐based cartilage repair with mesenchymal stem cells in a porcine model

Chang

Kuo

Lin

et al. 2011

Journal Orthopaedic Research

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This in vivo pilot study explored the use of mesenchymal stem cell (MSC) containing tissue engineering constructs in repair of osteochondral defects. Osteochondral defects were created in the medial condyles of both knees of 16 miniature pigs. One joint received a cell/collagen tissue engineering construct with or without pretreatment with transforming growth factor b (TGF-b) and the other joint from the same pig received no treatment or the gel scaffold only. Six months after surgery, in knees with no treatment, all defects showed contracted craters; in those treated with the gel scaffold alone, six showed a smooth gross surface, one a hypertrophic surface, and one a contracted crater; in those with undifferentiated MSCs, five defects had smooth, fully repaired surfaces or partially repaired surfaces, and one defect poor repair; in those with TGF-b-induced differentiated MSCs, seven defects had smooth, fully repaired surfaces or partially repaired surfaces, and three defects showed poor repair. In Pineda score grading, the group with undifferentiated MSC, but not the group with TGF-b-induced differentiated MSCs, had significantly lower subchondral, cell morphology, and total scores than the groups with no or gel-only treatment. The compressive stiffness was larger in cartilage without surgical treatment than the treated area within each group. In conclusion, this preliminary pilot study suggests that using undifferentiated MSCs might be a better approach than using TGF-b-induced differentiated MSCs for in vivo tissue engineered treatment of osteochondral defects. ß

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“…Exogenous undifferentiated MSCs such as those used by us have more homing and differentiation abilities than differentiated MSCs. 19,20 The more differentiated …”

Section: Discussionmentioning

confidence: 99%

Tissue engineering‐based cartilage repair with mesenchymal stem cells in a porcine model

Chang

Kuo

Lin

et al. 2011

Journal Orthopaedic Research

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“…Despite differences in the kinetics involved, blocking of CXCR4 on MSCs inhibits their recruitment and impaired wound healing Xu et al, 2013). However, in vitro expansion of BM MSCs may result in the downregulation of CXCR4 expression (Karp and Leng Teo, 2009). To guarantee robust recruitment of MSCs to the site of injury for the most effective therapeutic results, several studies have genetically modified MSCs to overexpress CXCR4, either by viral transfection Yang et al, 2013) or through a deficiency in negative transcription factor regulators (Xie et al, 2013).…”

Section: Mechanisms Of Msc and Pericyte Recruitment To Sites Of Injurymentioning

confidence: 99%

Pericytes, mesenchymal stem cells and their contributions to tissue repair

Wong

Rowley

Redpath

et al. 2015

Pharmacology & Therapeutics

152

110

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Regenerative medicine using mesenchymal stem cells for the purposes of tissue repair has garnered considerable public attention due to the potential of returning tissues and organs to a normal, healthy state after injury or damage has occurred. To achieve this, progenitor cells such as pericytes and bone marrow-derived mesenchymal stem cells can be delivered exogenously, mobilised and recruited from within the body or transplanted in the form organs and tissues grown in the laboratory from stem cells. In this review, we summarise the recent evidence supporting the use of endogenously mobilised stem cell populations to enhance tissue repair along with the use of mesenchymal stem cells and pericytes in the development of engineered tissues. Finally, we conclude with an overview of currently available therapeutic options to manipulate endogenous stem cells to promote tissue repair.

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“…Although not performed in this study, tracking the fate of implanted PBMMSC in vivo will be necessary in future work as homing of MSC in vivo is poorly understood. 44 Favorable results reported in this study were due, in part, to the gene delivery method we used. Electroporation is known to increase transgene copy number in the nucleus by several orders of magnitude, thus enhancing expression of the transgene product.…”

Section: Bone Marrow-derived Insulin Bioimplants Nkf Chen Et Almentioning

confidence: 81%

Insulin expressed from endogenously active glucose-responsive EGR1 promoter in bone marrow mesenchymal stromal cells as diabetes therapy

et al. 2010

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Advances in islet transplantation have encouraged efforts to create alternative insulin-secreting cells that overcome limitations associated with current therapies. We have recently demonstrated durable correction of murine and porcine diabetes by syngeneic and autologous implantation, respectively, of primary hepatocytes non-virally modified with a glucose-responsive promoter-regulated insulin transgene. As surgical procurement of hepatocytes may be clinically unappealing, we here describe primary bone marrow-derived mesenchymal stromal cells (BMMSC) as alternative insulinsecreting bioimplants. BMMSC are abundant and less invasively procured for clinical autologous transplantation. Electroporation achieved high transgene transfection efficiencies in human BMMSC (HBMMSC) and porcine BMMSC (PBMMSC). We transcriptomically identified an HBMMSC glucose-responsive promoter, EGR1. This endogenously active promoter drove rapid glucose-induced transgene secretions in BMMSC with near-physiological characteristics during static and kinetic induction assays simulating normal human islets. Preparatory to preclinical transplantation, PBMMSC transfected with the circular insulin transgene vector or stably integrated with the linearized vector were evaluated by intrahepatic or intraperitoneal xenotransplantation in streptozotocin-diabetic and non-diabetic NOD-SCID mice. Hyperglycemia, glucose tolerance and body weight were corrected in a dose-responsive manner. Hypoglycemia was not observed even in identically implanted non-diabetic mice. These results establish human EGR1 promoter-insulin construct-modified BMMSC as safe and efficient insulin-secreting bioimplants for diabetes treatment.

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Mesenchymal Stem Cell Homing: The Devil Is in the Details

Cited by 1,271 publications

References 97 publications

Tissue engineering‐based cartilage repair with mesenchymal stem cells in a porcine model

Tissue engineering‐based cartilage repair with mesenchymal stem cells in a porcine model

Pericytes, mesenchymal stem cells and their contributions to tissue repair

Insulin expressed from endogenously active glucose-responsive EGR1 promoter in bone marrow mesenchymal stromal cells as diabetes therapy

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