Faculty Opinions recommendation of Anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold in large animal model.

2009 ◽  
Author(s):  
Mats Brittberg
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Large Animal Model ◽  
Large Animal ◽  
Silk Scaffold ◽  
Anterior Cruciate

In vivo study of anterior cruciate ligament regeneration using mesenchymal stem cells and silk scaffold

Biomaterials ◽  
2008 ◽  
Vol 29 (23) ◽  
pp. 3324-3337 ◽  
Author(s):  
Hongbin Fan ◽  
Haifeng Liu ◽  
Eugene J.W. Wong ◽  
Siew L. Toh ◽  
James C.H. Goh
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
In Vivo Study ◽  
Silk Scaffold ◽  
Anterior Cruciate

scholarly journals A Translational Porcine Model for Human Cell–Based Therapies in the Treatment of Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Injury

2020 ◽  
Vol 48 (12) ◽  
pp. 3002-3012
Author(s):  
Thomas J. Kremen ◽  
Tina Stefanovic ◽  
Wafa Tawackoli ◽  
Khosrowdad Salehi ◽  
Pablo Avalos ◽  
...  
Keyword(s):  
Animal Model ◽  
Anterior Cruciate Ligament ◽  
Synovial Fluid ◽  
Human Cell ◽  
Bioluminescence Imaging ◽  
Cruciate Ligament ◽  
Acl Injury ◽  
Large Animal Model ◽  
Large Animal ◽  
Anterior Cruciate

Background: There is a high incidence of posttraumatic osteoarthritis (PTOA) after anterior cruciate ligament (ACL) injury, and these injuries represent an enormous health care economic burden. In an effort to address this unmet clinical need, there has been increasing interest in cell-based therapies. Purpose: To establish a translational large animal model of PTOA and demonstrate the feasibility of intra-articular human cell–based interventions. Study Design: Descriptive laboratory study. Methods: Nine Yucatan mini-pigs underwent unilateral ACL transection and were monitored for up to 12 weeks after injury. Interleukin 1 beta (IL-1β) levels and collagen breakdown were evaluated longitudinally using enzyme-linked immunosorbent assays of synovial fluid, serum, and urine. Animals were euthanized at 4 weeks (n = 3) or 12 weeks (n = 3) after injury, and injured and uninjured limbs underwent magnetic resonance imaging (MRI) and histologic analysis. At 2 days after ACL injury, an additional 3 animals received an intra-articular injection of 107 human bone marrow–derived mesenchymal stem cells (hBM-MSCs) combined with a fibrin carrier. These cells were labeled with the luciferase reporter gene (hBM-MSCs-Luc) as well as fluorescent markers and intracellular iron nanoparticles. These animals were euthanized on day 0 (n = 1) or day 14 (n = 2) after injection. hBM-MSC-Luc viability and localization were assessed using ex vivo bioluminescence imaging, fluorescence imaging, and MRI. Results: PTOA was detected as early as 4 weeks after injury. At 12 weeks after injury, osteoarthritis could be detected grossly as well as on histologic analysis. Synovial fluid analysis showed elevation of IL-1β shortly after ACL injury, with subsequent resolution by 2 weeks after injury. Collagen type II protein fragments were elevated in the synovial fluid and serum after injury. hBM-MSCs-Luc were detected immediately after injection and at 2 weeks after injection using fluorescence imaging, MRI, and bioluminescence imaging. Conclusion: This study demonstrates the feasibility of reproducing the chondral changes, intra-articular cytokine alterations, and body fluid biomarker findings consistent with PTOA after ACL injury in a large animal model. Furthermore, we have demonstrated the ability of hBM-MSCs to survive and express transgene within the knee joint of porcine hosts without immunosuppression for at least 2 weeks. Clinical Relevance: This model holds great potential to significantly contribute to investigations focused on the development of cell-based therapies for human ACL injury–associated PTOA in the future (see Appendix Figure A1 , available online).

scholarly journals Brazilian minipig as a large-animal model for basic research and stem cell-based tissue engineering. Characterization and in vitro differentiation of bone marrow-derived mesenchymal stem cells

2014 ◽  
Vol 22 (3) ◽  
pp. 218-227 ◽  
Author(s):  
Roberta Targa STRAMANDINOLI-ZANICOTTI ◽  
André Lopes CARVALHO ◽  
Carmen Lúcia Kuniyoshi REBELATTO ◽  
Laurindo Moacir SASSI ◽  
Maria Fernanda TORRES ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Basic Research ◽  
Large Animal Model ◽  
Large Animal ◽  
In Vitro Differentiation

Abstract WP145: Safety of Intra-Arterial Mesenchymal Stem Cells in a Large Animal Model of Stroke: A Dose Escalation Study

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mitsuyoshi Watanabe ◽  
Karen E Bates ◽  
Luis Guada ◽  
Kevin Ramdas ◽  
Aisha Khan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Dose Escalation ◽  
Cerebral Blood Volume ◽  
Maximum Tolerated Dose ◽  
Large Animal Model ◽  
Large Animal ◽  
Vessel Occlusion ◽  
Dose Escalation Study

Background: Despite the efficacy of thrombectomy for large vessel occlusion acute ischemic stroke (AIS) , ~50% of patients have significant residual deficits. Pre-clinical data on intra-arterially (IA) administered mesenchymal stem cells (MSCs) in stroke are promising and this approach is attractive for clinical application. While there is a concern for micro-occlusion with IA delivery due to the large size of MSCs, a dose of 1 x 10 5 MSCs given 24-48 hr in a rodent reperfusion middle cerebral artery occlusion (rMCAo) model has been shown to be safe and effective. As per STAIR recommendations, we performed a dose-escalation (DE) study of IA-MSCs in a large animal stroke model. Methods: An endovascular canine rMCAo model using retractable platinum coil for 60-120 min was established. At 48 hr post-rMCAo, allogeniec canine MSCs were delivered using a 0.0165” microcatheter in the ipsilateral upper cervical internal carotid artery in escalating doses (based on proportion of rodent to canine total cerebral blood volume). Serial MRIs and neurological deficit scoring (NDS) were performed over 30 days. Animals were euthanized at 15-30 d post-rMCAo and brains were harvested. Results: Female canines (n=13), age 12-36 months, weighing 22-26 kg received IA MSCs ranging from 5-80 x 10 6 (M). At doses of 5-40 M IA-MSCs no neurological worsening was observed. Serial NDS and stroke volume on MRI showed no increase post-IA-MSCs and actually showed progressive reduction. A higher numerical reduction was seen in the 10-40 M groups compared to 5 M. However, in the one canine receiving 80 M IA-MSCs, there was significant worsening of the MCA-area infarction and NDS due to microembolization at this higher dose. Gross examinations and histopathology of brain tissue were consistent with ischemia. The brain of a canine receiving 80 M cells showed differentially aged areas of necrosis supporting two ischemic events. Neuroblasts, doublecortin-positive cells, and neovascularization were observed in canine brains suggesting regenerative mechanisms. Conclusions: These data suggest that IA-MSCs are safe in a large animal model up to 40 M IA-MSCs and is the maximum tolerated dose in this DE study. Furthermore, our data suggests that up to 40 M IA-MSCs may be promising in exploring efficacy in AIS.

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