Intra-articular Injection of Mesenchymal Stromal Cells in Partially Torn Anterior Cruciate Ligaments in a Rat Model

Kanaya, Atsushi; Deie, Masataka; Adachi, Nobuo; Nishimori, Makoto; Yanada, Shinobu; Ochi, Mitsuo

doi:10.1016/j.arthro.2007.01.013

Cited by 104 publications

(97 citation statements)

References 20 publications

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“…There are several reports that have used different cell types to treat ligament injury such as myoblasts, bone marrow cells and mesenchymal stromal cells. 27,34,35 In the present study, we demonstrated that nLacZ transduced MDSCs could survive after being transplanted into an MCL injury site and that mRNA expression of rCol1A2 and rTeM were higher in the ligaments injected with MDSCs transduced with VEGF when compared to the MDSC transduced with sFLT1 and MCLs injected with PBS. From these results, we confirmed that MDSCs could contribute to ligament healing and that blocking VEGF with sFLT1 impedes the healing process.…”

Section: Discussionmentioning

confidence: 67%

Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament

Nishimori

Matsumoto

Ota

et al. 2011

Journal Orthopaedic Research

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We performed this study to investigate the therapeutic role of vascular endothelial growth factor (VEGF) in medial collateral ligament (MCL) healing. Murine muscle derived stem cells (MDSCs) obtained via the preplate technique were retrovirally transduced to express: (1) VEGF and nLacZ (MDSC-VEGF), (2) soluble fms-like tyrosine kinase-1 (sFLT1, a VEGF-specific antagonist) and nLacZ (MDSC-sFLT1), and (3) nLacZ (MDSC-nLacZ). After transecting the MCL of immunodeficient rats, 5 Â 10 5 cells of each of the transduction groups list above were transplanted into the MCL injury site. A control group was injected with phosphate-buffered saline (PBS) only. Immunohistochemical staining demonstrated that there were more Isolectin B4 and b-galactosidase double positive cells in the rats transplanted with MDSC-VEGF transduced cells than the other groups at week 1. Capillary density was significantly higher in the MDSC-VEGF group than the other groups at week 2; however, there were no significant differences in the biomechanical assessment between the MDSC-VEGF and MDSC-nLacZ groups. On the other hand, the MDSC-sFLT1 group revealed a lower capillary density than the other two groups and the functional ligament healing of the MDSC-sFLT1 group was significantly decreased compared to the other groups when assessed biomechanically. The findings of the present study suggest that angiogenesis plays a critical role in the healing process of injured MCL. ß

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Section: Discussionmentioning

confidence: 67%

Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament

Nishimori

Matsumoto

Ota

et al. 2011

Journal Orthopaedic Research

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“…In this regard, there have been encouraging models using precursor (i.e., mesenchymal) cells for the study of tissue repair. 17,18 Concerns remain, however, that organ reconstitution might be limited if the donor cells are not truly pluripotent or if the healing is just localized because of paracrine effects, cell fusion, or dedifferentiation of native cells. Similarly, for the tissue engineering approach using ECM scaffolds, the selection of which cells (somatic versus stem) is not straightforward.…”

Section: Discussionmentioning

confidence: 99%

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Ross

Williams²,

Hamazaki³

et al. 2009

Journal of the American Society of Nephrology

366

266

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The scarcity of transplant allografts for diseased organs has prompted efforts at tissue regeneration using seeded scaffolds, an approach hampered by the enormity of cell types and complex architectures. Our goal was to decellularize intact organs in a manner that retained the matrix signal for differentiating pluripotent cells. We decellularized intact rat kidneys in a manner that preserved the intricate architecture and seeded them with pluripotent murine embryonic stem cells antegrade through the artery or retrograde through the ureter. Primitive precursor cells populated and proliferated within the glomerular, vascular, and tubular structures. Cells lost their embryonic appearance and expressed immunohistochemical markers for differentiation. Cells not in contact with the basement membrane matrix became apoptotic, thereby forming lumens. These observations suggest that the extracellular matrix can direct regeneration of the kidney, and studies using seeded scaffolds may help define differentiation pathways.

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“…In addition, our findings revealed that tissues at the ACL rupture site, where vascularity is rich, possess an abundant number of stem cells when compared with the mid-substance region of the ligament. On the other hand, reports have shown the contribution and therapeutic potential of MSCs for ligament healing or tendon-bone repair [1,[50][51][52]. Lim and Soon et al performed bilateral ACL reconstruction in an animal model using grafts coated with MSCs suspended in fibrin glue [50,51].…”

mentioning

confidence: 99%

Isolation and Characterization of Human Anterior Cruciate Ligament-Derived Vascular Stem Cells

Matsumoto

Ingham

Mifune

et al. 2012

Stem Cells and Development

100

104

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The anterior cruciate ligament (ACL) usually fails to heal after rupture mainly due to the inability of the cells within the ACL tissue to establish an adequate healing process, making graft reconstruction surgery a necessity. However, some reports have shown that there is a healing potential of ACL with primary suture repair. Although some reports showed the existence of mesenchymal stem cell-like cells in human ACL tissues, their origin still remains unclear. Recently, blood vessels have been reported to represent a rich supply of stem/ progenitor cells with a characteristic expression of CD34 and CD146. In this study, we attempted to validate the hypothesis that CD34-and CD146-expressing vascular cells exist in hACL tissues, have a potential for multilineage differentiation, and are recruited to the rupture site to participate in the intrinsic healing of injured ACL. Immunohistochemistry and flow cytometry analysis of hACL tissues demonstrated that it contains significantly more CD34 and CD146-positive cells in the ACL ruptured site compared with the noninjured midsubstance. CD34 + CD45 -cells isolated from ACL ruptured site showed higher expansionary potentials than CD146 + CD45 -and CD34 -CD146 -CD45 -cells, and displayed higher differentiation potentials into osteogenic, adipogenic, and angiogenic lineages than the other cell populations. Immunohistochemistry of fetal and adult hACL tissues demonstrated a higher number of CD34 and CD146-positive cells in the ACL septum region compared with the midsubstance. In conclusion, our findings suggest that the ACL septum region contains a population of vascular-derived stem cells that may contribute to ligament regeneration and repair at the site of rupture.

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Intra-articular Injection of Mesenchymal Stromal Cells in Partially Torn Anterior Cruciate Ligaments in a Rat Model

Cited by 104 publications

References 20 publications

Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament

Role of angiogenesis after muscle derived stem cell transplantation in injured medial collateral ligament

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Isolation and Characterization of Human Anterior Cruciate Ligament-Derived Vascular Stem Cells

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