scholarly journals The regenerative effect of different growth factors and platelet lysate on meniscus cells and mesenchymal stromal cells and proof‐of‐concept with a functionalized meniscus implant Growth factors for enhancement of meniscus regeneration

2021 ◽  
Author(s):  
Michella H. Hagmeijer ◽  
Jasmijn V. Korpershoek ◽  
João F. Crispim ◽  
Li‐Ting Chen ◽  
Pascal Jonkheijm ◽  
...  
Keyword(s):  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Platelet Lysate ◽  
Proof Of Concept ◽  
Regenerative Effect ◽  
Meniscus Regeneration ◽  
Meniscus Cells

scholarly journals Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashley A. Krull ◽  
Deborah O. Setter ◽  
Tania F. Gendron ◽  
Sybil C. L. Hrstka ◽  
Michael J. Polzin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Scale ◽  
Therapeutic Benefit ◽  
Protein Levels ◽  
Genes Encoding ◽  
Intrathecal Space

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

scholarly journals Platelet-Lysate-Expanded Mesenchymal Stromal Cells for the Treatment of Resistant GVHD

2011 ◽  
Vol 17 (2) ◽  
pp. S169
Author(s):  
G. Lucchini ◽  
E. Dander ◽  
A. Rovelli ◽  
A. Balduzzi ◽  
S. Bonanomi ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Platelet Lysate

Cell culture confluency level and the variability of platelet lysate pools impact the readout of the ostegenic differentiation assay of mesenchymal stromal cells

Cytotherapy ◽  
2017 ◽  
Vol 19 (5) ◽  
pp. S164-S165
Author(s):  
A. Laitinen ◽  
T. Kaartinen ◽  
S. Oja ◽  
M. Korhonen ◽  
K. Alfthan ◽  
...  
Keyword(s):  
Cell Culture ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Platelet Lysate

scholarly journals Inactivated Platelet Lysate Supports Proliferation and Immunomodulant Characteristics Of Mesenchymal Stromal Cells in GMP Culture Condition

2020 ◽  
Author(s):  
Katia Mareschi ◽  
Sara Castiglia ◽  
Aloe Adamini ◽  
Deborah Rustichelli ◽  
Elena Marini ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Good Alternative ◽  
Good Manufacturing Practice ◽  
Platelet Lysate ◽  
T Cell Subsets ◽  
Cytokine Release ◽  
Pathogen Inactivation ◽  
Advanced Therapy

For their clinical use Mesenchymal Stromal Cells (MSCs), isolated from bone marrow (BM-MSCs) are considered Advanced Therapy Medicinal Products (ATMP) and need to be produced according to Good Manufacturing Practice (GMP). Human platelet lysate (HPL) represents a good GMP-compliant alternative to animal serum and after pathogen inactivation with Psoralen was more efficient and safer to produce MSCs in GMP. In this study MSCs cultivated in FBS (FBS-MSC) or inactivated HPL (iHPL-MSC), were compared for their immunomodulant properties. In particular, the effects of MSCs on: 1)proliferation of total Lymphocytes (Ly) and on naïve T Ly subsets induced to differentiate versus Th1 and Th2 Ly; 2) the immunophenotype of different T cell subsets; 3)the cytokine release to verify Th1, Th2 and Th17 polarization were analyzed by using in vitro co-culture system. We observed that iHPL-MSCs showed the same immunomodulant properties observed in the FBS-MSCs co-cultures. Although, a more efficient effect on the increase of naïve T cells and, in the Th1 cytokine release related to iHPL was observed. This study confirms that iHPL, used as medium supplement, may be considered a good alternative to FBS for a GMP-compliant MSC expansion to preserve their immunomodulant proprieties.

Comparative Analysis of Biological and Functional Properties of Bone Marrow Mesenchymal Stromal Cells Expanded in Media with Different Platelet Lysate Content

2018 ◽  
Vol 205 (4) ◽  
pp. 226-239 ◽  
Author(s):  
Marijana Skific ◽  
Mirna Golemovic ◽  
Kristina Crkvenac-Gornik ◽  
Radovan Vrhovac ◽  
Branka Golubic Cepulic
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immunological Tolerance ◽  
Biological Properties ◽  
Platelet Lysate ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Significant Difference

Due to their ability to induce immunological tolerance in the recipient, mesenchymal stromal cells (MSCs) have been utilized in the treatment of various hematological and immune- and inflammation-mediated diseases. The clinical application of MSCs implies prior in vitro expansion that usually includes the use of fetal bovine serum (FBS). The present study evaluated the effect of different platelet lysate (PL) media content on the biological properties of MSCs. MSCs were isolated from the bone marrow of 13 healthy individuals and subsequently expanded in three different culture conditions (10% PL, 5% PL, 10% FBS) during 4 passages. The cells cultured in different conditions had comparable immunophenotype, clonogenic potential, and differentiation capacity. However, MSC growth was significantly enhanced in the presence of PL. Cultures supplemented with 10% PL had a higher number of cumulative population doublings in all passages when compared to the 5% PL condition (p < 0.03). Such a difference was also observed when 10% PL and 10% FBS conditions were compared (p < 0.005). A statistically significant difference in population doubling time was determined only between the 10% PL and 10% FBS conditions (p < 0.005). Furthermore, MSCs cultured in 10% PL were able to cause a 66.9% reduction of mitogen-induced lymphocyte proliferation. Three chromosome aberrations were detected in PL conditions. Since two changes occurred in the same do nor, it is possible they were donor dependent rather than caused by the culture condition. These findings demonstrate that a 10% PL condition enables a higher yield of MSCs within a shorter time without altering MSC properties, and should be favored over the 5% PL condition.

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