Comparative analysis of in vitro proliferative, migratory and pro-angiogenic potentials of bovine fetal mesenchymal stem cells derived from bone marrow and adipose tissue

Jervis, Miguel; Huaman, Olger; Cahuascanco, Berly; Bahamonde, Javiera; Cortez, Jahaira; Arias, J.I.; Torres, CG; Peralta, Oscar A.

doi:10.1007/s11259-019-09757-9

Cited by 15 publications

(17 citation statements)

References 44 publications

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“…Bovine fetal AT-MSC isolation and culture. AT-MSCs were harvested from fetal AT present in the abdominal omentum from male bovine fetuses (n = 9; 7-8 months of gestation) collected at a local abattoir [9][10][11] . Approximately 10 g of AT were isolated under aseptic conditions and deposited in PBS supplemented with 100 IU/mL penicillin, 100 μg/mL streptomycin and 2.5 μg/mL amphotericin B (Hyclone, Thermo Fisher Scientific, UT, USA).…”

Section: Methodsmentioning

confidence: 99%

“…RNA extraction, cDNA synthesis and quantitative PCR. Purification of total RNA from PBLs was performed using a GeneJET purification kit (Thermo Scientific, Vilnus, Lithuania), following the manufacturer's instructions [9][10][11] . Total RNA was extracted using GeneJET RNA purification kit (Thermo Scientific) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…We have recently reported that stimulation of bovine fetal AT-MSCs with inflammatory interferon γ (IFNγ) induce up-regulation of immunomodulatory factors indolamine 2,3-dioxygenase (IDO) and interleukin 6 (IL-6) 9 . In addition, bovine fetal AT-MSCs are able to induce angiogenesis under in vitro conditions, which may be mediated by expression of vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANGPT1) 10 . Moreover, conditioned media from bovine fetal AT-MSCs induce an anti-proliferative effect against mastitis-causing S. aureus, which may be mediated by antibacterial peptides (AP) defensin β1 (DEFβ1) and NK Lysin 11 .…”

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confidence: 99%

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Safety and efficacy of a mesenchymal stem cell intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis

Peralta

Carrasco

Vieytes

et al. 2020

Sci Rep

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Although, antibiotics are effective in the treatment of bovine mastitis, they do not address the regeneration of mammary glandular tissue and have been associated to the increment in antimicrobial resistance worldwide. Considering the necessity of alternative therapies for this disease of high economic impact and the reported regenerative and antibacterial effects of mesenchymal stem cell (MSCs), we evaluated the safety and efficacy of an allogenic MSC-based intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis. In a safety trial, heifers were inoculated intramammarily with a 2.5 × 10 7 -suspension of bovine fetal AT-MSCs on experimental days 1 and 10. Animals were evaluated clinically on a daily basis during a 20-day experimental period and blood samples were collected for hemogram determination and peripheral blood leukocytes (PBLs) isolation. In an efficacy trial, Holstein Friesian cows were inoculated with S. aureus and treated intramammarily with vehicle (NEG; days 4 and 10), antibiotics (ATB; days 4 and 5) or a suspension of 2.5 × 10 7 AT-MSCs (MSC; days 4 and 5). Cows were clinically evaluated daily and milk samples were collected for somatic cell count (SCC) and colony forming units (CFU). Blood samples were collected for serum haptoglobin and amyloid A determination. Intramammary administration of two doses of bovine fetal AT-MSCs in healthy cows did not induce changes in clinical or hematological variables, and gene expression profiles in PBLs associated to activation (CD4, CD8, CD25, CD62L and CD69) and proinflammatory cytokines (CCL2, CCL5, IL2, CXCL3, IFNγ, and TNFα). Quarters of MSC group of cows had similar SCC log/mL in milk compared to infected quarters of ATB or NEG cows. However, quarters of MSC cows had lower CFU log/mL in milk compared to quarters of NEG cows. Intramammarily inoculation of repeated doses of 2.5 × 10 7 allogenic AT-MSCs did not induce clinical or immunological response in healthy cows. Moreover, MSC-intramammary treatment reduced bacterial count in milk of cows with S. aureus clinical mastitis compared to untreated cows. This work provides initial evidence for the safety and efficacy of an allogenic MSC-based intramammary therapy for the treatment of bovine mastitis.the remaining two mammary quarters, a 3 mL solution of ringer lactate was administered as control (vehicle). Animals were evaluated clinically on a daily basis during a 20-Day experimental period. Heart rate (HR), respiratory rate (RR), and rectal temperature (RT) were determined. The clinical evaluation of the mammary gland was based on a previously published method that includes the observation of volume increase, firmness, signs of pain and milk secretion 13 . In addition, the mammary surface temperature (MST) of each quarter was quantified using a portable thermograph (Fluke VT02 Washington, USA). Mammary temperature difference (MTD) was calculated by subtracting MST from quarters inoculated with AT-MSCs from quarters inoculated with vehicle. Blood samples were ...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Safety and efficacy of a mesenchymal stem cell intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis

Peralta

Carrasco

Vieytes

et al. 2020

Sci Rep

Self Cite

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“…After stimulating these MSCs with lipopolysaccharide (LPS), an increased 397 proteins were detected in the secretome, particularly those proteins involved in immunomodulation and tissue repair, leading the authors to conclude that these cow MSCs could be useful to treat reproductive diseases of cattle (de Moraes et al, 2017). Additional in vitro studies showed that the secretome from fetal cow MSC reduced the growth of S. aureus (Cahuascanco et al, 2019) and promoted endothelial cells to form tubules, an in vitro proxy for angiogenic potential (Jervis et al, 2019). Based on currently available data, the cow MSC secretome has been proposed as a treatment for mastitis, wound healing, nerve injuries, degenerative joint diseases and other diseases of the skeletal system, as well as diabetes mellitus (Gugjoo et al, 2019;Hill et al, 2019).…”

Section: Naïve Large Animal Mscsmentioning

confidence: 99%

Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

Harman

Marx

Walle

2021

Front. Cell Dev. Biol.

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The therapeutic potential of the mesenchymal stromal cell (MSC) secretome, consisting of all molecules secreted by MSCs, is intensively studied. MSCs can be readily isolated, expanded, and manipulated in culture, and few people argue with the ethics of their collection. Despite promising pre-clinical studies, most MSC secretome-based therapies have not been implemented in human medicine, in part because the complexity of bioactive factors secreted by MSCs is not completely understood. In addition, the MSC secretome is variable, influenced by individual donor, tissue source of origin, culture conditions, and passage. An increased understanding of the factors that make up the secretome and the ability to manipulate MSCs to consistently secrete factors of biologic importance will improve MSC therapy. To aid in this goal, we can draw from the wealth of information available on secreted factors from MSC isolated from veterinary species. These translational animal models will inspire efforts to move human MSC secretome therapy from bench to bedside.

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“…Bone marrow (BM) has been the main source of MSCs for research and clinical trials, however, MSCs have also been isolated from nearly every tissue, including adipose tissue (AT), umbilical cord blood, dental pulp, synovial fluid, and amniotic fluid, among many others. All these tissues present variability in their secreted factors/signals and cellular components, generating different conditions, and physiological niches that can affect the behavior of MSCs, such as their proliferative activity ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Bovine Fetal Mesenchymal Stem Cells Obtained From Omental Adipose Tissue and Placenta Are More Resistant to Cryoprotectant Exposure Than Those From Bone Marrow

et al. 2021

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Recent studies have shown promise for the development of cellular therapies with mesenchymal stem cells (MSCs) in livestock species, specifically bovines, and cryopreservation is highly relevant for the advancement of these applications. The use of permeable and/or non-permeable cryoprotectant solutions is necessary to reduce cell damage during freezing and thawing, but these same compounds can also cause negative effects on MSCs and their therapeutic properties. Another important factor to consider is the tissue source of MSCs, since it is now known that MSCs from different tissues of the same individual do not behave the same way, so optimizing the type and concentration of cryoprotectants for each cell type is essential to achieve a large and healthy population of MSCs after cryopreservation. Furthermore, sources of MSCs that could provide great quantities, non-invasively and without ethical concerns, such as placental tissue, have great potential for the development of regenerative medicine in livestock species, and have not been thoroughly evaluated. The objective of this study was to compare the viability of bovine fetal MSCs extracted from bone marrow (BM), adipose tissue (AT), and placenta (PT), following their exposure (15 and 30 min) to several solutions of permeable (dimethyl sulfoxide and ethylene glycol) and non-permeable (trehalose) cryoprotectants. Viability assays were performed with Trypan Blue to assess post-exposure plasma membrane integrity. The apoptotic potential was estimated analyzing the mRNA abundance of BAX and BCL-2 genes using quantitative rt-PCR. Based on the results of the study, BM-MSC exhibited significantly lower viability compared to AT-MSC and PT-MSC, at both 15 and 30 min of exposure to cryoprotectant solutions. Nevertheless, viability did not differ among treatments for any of the cell types or timepoints studied. BCL-2 expression was higher in BM-MSC compared to AT-MSC, however, BAX/BCL-2 ratio did not differ. In conclusion, AT-MSC and PT-MSC were more resistant that BM-MSC, which showed higher sensitivity to experimental conditions, regardless of the exposure times, and cryoprotectant solutions used in the study.

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Comparative analysis of in vitro proliferative, migratory and pro-angiogenic potentials of bovine fetal mesenchymal stem cells derived from bone marrow and adipose tissue

Cited by 15 publications

References 44 publications

Safety and efficacy of a mesenchymal stem cell intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis

Safety and efficacy of a mesenchymal stem cell intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis

Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

Bovine Fetal Mesenchymal Stem Cells Obtained From Omental Adipose Tissue and Placenta Are More Resistant to Cryoprotectant Exposure Than Those From Bone Marrow

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