Research using Mesenchymal Stem/Stromal Cells: quality metric towards developing a reference material

Tanavde, Vivek; Vaz, Candida; Rao, Mahendra S.; Vemuri, Mohan C.; Pochampally, Radhika

doi:10.1016/j.jcyt.2015.07.008

Cited by 36 publications

(25 citation statements)

References 44 publications

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“…Several studies address the potential utility of a cellular universal ruler for MSC potency assays (Bloom et al, 2015; Deans, 2015; Salem et al, 2015; Tanavde et al, 2015; Viswanathan et al, 2014). However, MSCs’ mechanism of action in vivo may well involve the effect of a plurality of effector pathways with synergistic and overlapping functionalities whose integrative effects are not completely understood when examined for use in distinct clinical uses.…”

Section: Discussionmentioning

confidence: 99%

Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach

et al. 2018

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SUMMARY Assays that can characterize MSC immune potency need to be identified for use in advanced clinical trials. MSCs possess a number of putative regenerative and immunomodulatory properties, and an assay matrix approach may best capture involved effector pathways. We have tested two assay systems to measure the potency of MSCs derived from human subjects: MSC secretome analysis and a quantitative RNA-based array for genes specific to immunomodulatory and homing properties of MSCs. Secretome analysis identified a unique cytokine signature that is upregulated by MSCs or downregulated in responder PBMCs and correlated with T cell suppression. Use of interferon-γ as a surrogate for the action of activated PBMCs on MSCs served as an alternative for the use of human PBMCs as responder cells in a potency assay. Our approach and results define and simplify the multifunctional or matrix responses of MSCs and may serve as a platform for robust potency analysis.

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Section: Discussionmentioning

confidence: 99%

Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach

et al. 2018

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“…The actual patient populations requiring hMSC therapies will likely be of wide age range and suffer from illness, so inter‐patient variability in quality of cell material will result from age and disease status. Other sources of variability in hMSC quality arise from variability in isolation and processing protocols . Therefore, the rationale underlying our work was to address observe process variability independent of donor age and gender.…”

Section: Discussionmentioning

confidence: 99%

Donor Variability in Growth Kinetics of Healthy hMSCs Using Manual Processing: Considerations for Manufacture of Cell Therapies

Detela

Bain

Kim

et al. 2018

Biotechnology Journal

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Human mesenchymal stromal cells (hMSCs) are excellent candidates for cell therapy but their expansion to desired clinical quantities can be compromised by ex vivo processing, due to differences between donor material and process variation. The aim of this article is to characterize growth kinetics of healthy baseline "reference" hMSCs using typical manual processing. Bone-marrow derived hMSCs from ten donors are isolated based on plastic adherence, expanded, and analyzed for their growth kinetics until passage 4. Results indicate that hMSC density decreases with overall time in culture (p < 0.001) but no significant differences are observed between successive passages after passage 1. In addition, fold increase in cell number dropped between passage 1 and 2 for three batches, which correlated to lower performance in total fold increase and expansion potential of these batches, suggesting that proliferative ability of hMSCs can be predicted at an early stage. An indicative bounded operating window is determined between passage 1 and 3 (PDL < 10), despite the high inter-donor variability present under standardized hMSC expansion conditions used. hMSC growth profile analysis will be of benefit to cell therapy manufacturing as a tool to predict culture performance and attainment of clinically-relevant yields, therefore stratifying the patient population based on early observation.

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“…Despite these promising outcomes, drawbacks to using hBMSCs and hADSCs include associated donor site morbidity and low cell yields during harvest requiring significant ex vivo expansion before implantation. Additionally, early clinical investigations using MSCs for orthopaedic applications suggest that administration of large quantities of adult MSCs (ie, ≥10 × 10 7 per dose) are required to realize improved outcomes 4,13,19,29 ; such quantities are not easily achieved with hBMSCs or hADSCs. Identifying alternative MSC sources that can yield a significant number of cells at the time of harvest and that demonstrate the ability to form bone and cartilage tissue would be clinically advantageous.…”

mentioning

confidence: 99%

Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells

et al. 2017

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Background Therapeutic efficacy of various mesenchymal stromal cell (MSC) types for orthopaedic applications is currently being investigated. While the concept of MSC therapy is well grounded in the basic science of healing and regeneration, little is known about individual MSC populations in terms of their propensity to promote the repair and/or regeneration of specific musculoskeletal tissues. Two promising MSC sources, adipose and amnion, have each demonstrated differentiation and extracellular matrix (ECM) production in the setting of musculoskeletal tissue regeneration. However, no study to date has directly compared the differentiation potential of these 2 MSC populations. Purpose To compare the ability of human adipose- and amnion-derived MSCs to undergo osteogenic and chondrogenic differentiation. Study Design Controlled laboratory study. Methods MSC populations from the human term amnion were quantified and characterized via cell counting, histologic assessment, and flow cytometry. Differentiation of these cells in comparison to commercially purchased human adipose-derived mesenchymal stromal cells (hADSCs) in the presence and absence of differentiation media was evaluated via reverse transcription polymerase chain reaction (PCR) for bone and cartilage gene transcript markers and histology/immunohistochemistry to examine ECM production. Analysis of variance and paired t tests were performed to compare results across all cell groups investigated. Results The authors confirmed that the human term amnion contains 2 primary cell types demonstrating MSC characteristics—(1) human amniotic epithelial cells (hAECs) and (2) human amniotic mesenchymal stromal cells (hAMSCs)—and each exhibited more than 90% staining for MSC surface markers (CD90, CD105, CD73). Average viable hAEC and hAMSC yields at harvest were 2.3 × 106 ± 3.7 × 105 and 1.6 × 106 ± 4.7 × 105 per milliliter of amnion, respectively. As well, hAECs and hAMSCs demonstrated significantly greater osteocalcin (P = .025), aggrecan (P < .0001), and collagen type 2 (P = .044) gene expression compared with hADSCs, respectively, after culture in differentiation medium. Moreover, both hAECs and hAMSCs produced significantly greater quantities of mineralized (P < .0001) and cartilaginous (P = .0004) matrix at earlier time points compared with hADSCs when cultured under identical osteogenic and chondrogenic differentiation conditions, respectively. Conclusion Amnion-derived MSCs demonstrate a greater differentiation potential toward bone and cartilage compared with hADSCs. Clinical Relevance Amniotic MSCs may be the source of choice in the regenerative treatment of bone or osteochondral musculoskeletal disease. They show significantly higher yields and better differentiation toward these tissues than MSCs derived from adipose.

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Research using Mesenchymal Stem/Stromal Cells: quality metric towards developing a reference material

Cited by 36 publications

References 44 publications

Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach

Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach

Donor Variability in Growth Kinetics of Healthy hMSCs Using Manual Processing: Considerations for Manufacture of Cell Therapies

Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells

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