Labelling and Tracking of Human Mesenchymal Stromal Cells in Preclinical Studies and Large Animal Models of Degenerative Diseases

2014 ◽  
Vol 9 (5) ◽  
pp. 444-450 ◽  
Author(s):  
Martin Vaegler ◽  
Jan Maerz ◽  
Bastian Amend ◽  
Luis Silva ◽  
Julia Mannheim ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Animal ◽  
Preclinical Studies ◽  
Degenerative Diseases ◽  
Human Mesenchymal Stromal Cells ◽  
Large Animal Models

Production of Adeno-Associated Virus Vectors in Cell Stacks for Preclinical Studies in Large Animal Models

10.3791/62727 ◽  
2021 ◽  
Author(s):  
Amira D. Rghei ◽  
Brenna A. Y. Stevens ◽  
Sylvia P. Thomas ◽  
Jacob G. E. Yates ◽  
Benjamin M. McLeod ◽  
...  
Keyword(s):  
Animal Models ◽  
Large Animal ◽  
Preclinical Studies ◽  
Adeno Associated Virus ◽  
Virus Vectors ◽  
Large Animal Models

scholarly journals Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Eder Zucconi ◽  
Natassia Moreira Vieira ◽  
Carlos Roberto Bueno ◽  
Mariane Secco ◽  
Tatiana Jazedje ◽  
...  
Keyword(s):  
Animal Models ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Muscle Cells ◽  
Muscular Dystrophies ◽  
Human Umbilical Cord ◽  
Preclinical Studies ◽  
Cell Based Therapy ◽  
Umbilical Cord Tissue

Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cellsin vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cellsin vivoin two animal models of PMDs. In order to address this question we injected (1) human umbilical cord tissue (hUCT) MSCs into the caudal vein ofSJLmice; (2) hUCT and canine umbilical cord vein (cUCV) MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies.

scholarly journals Preclinical Models for Skeletal Research: How Commonly Used Species Mimic (or Don’t) Aspects of Human Bone

2017 ◽  
Vol 45 (7) ◽  
pp. 851-854 ◽  
Author(s):  
Matthew R. Allen
Keyword(s):  
Animal Models ◽  
Bone Growth ◽  
Human Bone ◽  
Large Animal ◽  
Preclinical Studies ◽  
Preclinical Models ◽  
Biological Regulation ◽  
Large Animal Models ◽  
Age Related ◽  
Age Related Changes

Preclinical studies play an indispensable role in exploring the biological regulation of the musculoskeletal system. They are required in all drug development pipelines where both small and large animal models are needed to understand efficacy and side effects. This brief review highlights 4 aspects of human bone, longitudinal bone growth, intracortical remodeling, collagen/mineral interface, and age-related changes, and discusses how various animal models recapitulate (or don’t) these aspects of human skeletal physiology.

scholarly journals Markers for Characterization of Bone Marrow Multipotential Stromal Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sally A. Boxall ◽  
Elena Jones
Keyword(s):  
Bone Marrow ◽  
Animal Models ◽  
Stromal Cells ◽  
Cartilage Tissue ◽  
Proliferative Potential ◽  
Large Animal ◽  
Native Bone ◽  
Large Animal Models

Given the observed efficacy of culture-expanded multipotential stromal cells, also termed mesenchymal stem cells (MSCs), in the treatment of graft-versus host and cardiac disease, it remains surprising that purity and potency characterization of manufactured cell batches remains rather basic. In this paper, we will initially discuss surface and molecular markers that were proposed to serve as the indicators of the MSC potency, in terms of their proliferative potential or the ability to differentiate into desired lineages. The second part of this paper will be dedicated to a critical discussion of surface markers of uncultured (i.e., native) bone marrow (BM) MSCs. Although no formal consensus has yet been reached on which markers may be best suited for prospective BM MSC isolation, markers that cross-react with MSCs of animal models (such as CD271 and W8-B2/MSCA-1) may have the strongest translational value. Whereas small animal models are needed to discover thein vivofunction on these markers, large animal models are required for safety and efficacy testing of isolated MSCs, particularly in the field of bone and cartilage tissue engineering.

scholarly journals Multi-pronged approach to human mesenchymal stromal cells senescence quantification with a focus on label-free methods

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weichao Zhai ◽  
Jerome Tan ◽  
Tobias Russell ◽  
Sixun Chen ◽  
Dennis McGonagle ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Preclinical Model ◽  
Label Free ◽  
Current Standard ◽  
Differentiation Potential ◽  
Human Mesenchymal Stromal Cells ◽  
Endogenous Fluorophores

AbstractHuman mesenchymal stromal cells (hMSCs) have demonstrated, in various preclinical settings, consistent ability in promoting tissue healing and improving outcomes in animal disease models. However, translation from the preclinical model into clinical practice has proven to be considerably more difficult. One key challenge being the inability to perform in situ assessment of the hMSCs in continuous culture, where the accumulation of the senescent cells impairs the culture’s viability, differentiation potential and ultimately leads to reduced therapeutic efficacies. Histochemical $$\upbeta $$ β -galactosidase staining is the current standard for measuring hMSC senescence, but this method is destructive and not label-free. In this study, we have investigated alternatives in quantification of hMSCs senescence, which included flow cytometry methods that are based on a combination of cell size measurements and fluorescence detection of SA-$$\upbeta $$ β -galactosidase activity using the fluorogenic substrate, C$${_{12}}$$ 12 FDG; and autofluorescence methods that measure fluorescence output from endogenous fluorophores including lipopigments. For identification of senescent cells in the hMSC batches produced, the non-destructive and label-free methods could be a better way forward as they involve minimum manipulations of the cells of interest, increasing the final output of the therapeutic-grade hMSC cultures. In this work, we have grown hMSC cultures over a period of 7 months and compared early and senescent hMSC passages using the advanced flow cytometry and autofluorescence methods, which were benchmarked with the current standard in $$\upbeta $$ β -galactosidase staining. Both the advanced methods demonstrated statistically significant values, (r = 0.76, p $$\le $$ ≤ 0.001 for the fluorogenic C$${_{12}}$$ 12 FDG method, and r = 0.72, p $$\le $$ ≤ 0.05 for the forward scatter method), and good fold difference ranges (1.120–4.436 for total autofluorescence mean and 1.082–6.362 for lipopigment autofluorescence mean) between early and senescent passage hMSCs. Our autofluroescence imaging and spectra decomposition platform offers additional benefit in label-free characterisation of senescent hMSC cells and could be further developed for adoption for future in situ cellular senescence evaluation by the cell manufacturers.

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