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Fulltext The current landscape of the mesenchymal stromal cell secretome: A new paradigm for cell-free regeneration

Konala VB, Mamidi MK, Bhonde R, Das AK, Pochampally R, Pal R

Cytotherapy, 2016 Jan;18(1):13-24.
PMID: 26631828 DOI: 10.1016/j.jcyt.2015.10.008

The unique properties of mesenchymal stromal/stem cells (MSCs) to self-renew and their multipotentiality have rendered them attractive to researchers and clinicians. In addition to the differentiation potential, the broad repertoire of secreted trophic factors (cytokines) exhibiting diverse functions such as immunomodulation, anti-inflammatory activity, angiogenesis and anti-apoptotic, commonly referred to as the MSC secretome, has gained immense attention in the past few years. There is enough evidence to show that the one important pathway by which MSCs participate in tissue repair and regeneration is through its secretome. Concurrently, a large body of MSC research has focused on characterization of the MSC secretome; this includes both soluble factors and factors released in extracellular vesicles, for example, exosomes and microvesicles. This review provides an overview of our current understanding of the MSC secretome with respect to their potential clinical applications.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology
The proliferation and tenogenic differentiation potential of bone marrow-derived mesenchymal stromal cell are influenced by specific uniaxial cyclic tensile loading conditions

Nam HY, Pingguan-Murphy B, Amir Abbas A, Mahmood Merican A, Kamarul T

Biomech Model Mechanobiol, 2015 Jun;14(3):649-63.
PMID: 25351891 DOI: 10.1007/s10237-014-0628-y

It has been previously demonstrated that mechanical stimuli are important for multipotent human bone marrow-derived mesenchymal stromal cells (hMSCs) to maintain good tissue homeostasis and even to enhance tissue repair processes. In tendons, this is achieved by promoting the cellular proliferation and tenogenic expression/differentiation. The present study was conducted to determine the optimal loading conditions needed to achieve the best proliferation rates and tenogenic differentiation potential. The effects of mechanical uniaxial stretching using different rates and strains were performed on hMSCs cultured in vitro. hMSCs were subjected to cyclical uniaxial stretching of 4, 8 or 12 % strain at 0.5 or 1 Hz for 6, 24, 48 or 72 h. Cell proliferation was analyzed using alamarBlue[Formula: see text] assay, while hMSCs differentiation was analyzed using total collagen assay and specific tenogenic gene expression markers (type I collagen, type III collagen, decorin, tenascin-C, scleraxis and tenomodulin). Our results demonstrate that the highest cell proliferation is observed when 4 % strain [Formula: see text] 1 Hz was applied. However, at 8 % strain [Formula: see text] 1 Hz loading, collagen production and the tenogenic gene expression were highest. Increasing strain or rates thereafter did not demonstrate any significant increase in both cell proliferation and tenogenic differentiation. In conclusion, our results suggest that 4 % [Formula: see text] 1 Hz cyclic uniaxial loading increases cell proliferation, but higher strains are required for superior tenogenic expressions. This study suggests that selected loading regimes will stimulate tenogenesis of hMSCs.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Fulltext A comparative study on in vitro osteogenic priming potential of electron spun scaffold PLLA/HA/Col, PLLA/HA, and PLLA/Col for tissue engineering application

Balaji Raghavendran HR, Puvaneswary S, Talebian S, Murali MR, Raman Murali M, Naveen SV, et al.

PLoS One, 2014;9(8):e104389.
PMID: 25140798 DOI: 10.1371/journal.pone.0104389

A comparative study on the in vitro osteogenic potential of electrospun poly-L-lactide/hydroxyapatite/collagen (PLLA/HA/Col, PLLA/HA, and PLLA/Col) scaffolds was conducted. The morphology, chemical composition, and surface roughness of the fibrous scaffolds were examined. Furthermore, cell attachment, distribution, morphology, mineralization, extracellular matrix protein localization, and gene expression of human mesenchymal stromal cells (hMSCs) differentiated on the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The electrospun scaffolds with a diameter of 200-950 nm demonstrated well-formed interconnected fibrous network structure, which supported the growth of hMSCs. When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds presented a higher density of viable cells and significant upregulation of genes associated with osteogenic lineage, which were achieved without the use of specific medium or growth factors. These results were supported by the elevated levels of calcium, osteocalcin, and mineralization (P<0.05) observed at different time points (0, 7, 14, and 21 days). Furthermore, electron microscopic observations and fibronectin localization revealed that PLLA/Col/HA scaffolds exhibited superior osteoinductivity, when compared with PLLA/Col or PLLA/HA scaffolds. These findings indicated that the fibrous structure and synergistic action of Col and nano-HA with high-molecular-weight PLLA played a vital role in inducing osteogenic differentiation of hMSCs. The data obtained in this study demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be supportive for stem cell based therapies for bone repair, when compared with the other two scaffolds.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Effect of culture media on expansion properties of human umbilical cord matrix-derived mesenchymal cells

Salehinejad P, Alitheen NB, Nematollahi-Mahani SN, Ali AM, Omar AR, Janzamin E, et al.

Cytotherapy, 2012 Sep;14(8):948-53.
PMID: 22587592 DOI: 10.3109/14653249.2012.684377

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) have been isolated from a number of different tissues, including umbilical cord. Because of the lack of a uniform approach to human umbilical cord matrix-derived mesenchymal (hUCM) cell expansion, we attempted to identify the optimum conditions for the production of a high quantity of hUCM cells by comparing two media.
METHODS: We compared the ability of Dulbecco's Modified Eagle's Medium/F12 (DMEM/F12) and Alpha Minimum Essential Medium (α-MEM) with Glutamax (GL) (α-MEM/GL) to expand hUCM cells. For this purpose, hUCM cells were cultured in plates containing different culture media supplemented with 10% fetal bovine serum (FBS). Culture dishes were left undisturbed for 10-14 days to allow propagation of the newly formed hUCM cells. The expansion properties, CD marker expression, differentiation potential, population doubling time (PDT) and cell activity were compared between the two groups.
RESULTS: The hUCM cells harvested from each group were positive for MSC markers, including CD44, CD90 and CD105, while they were negative for the hematopoietic cell surface marker CD34. Differentiation into adipogenic and osteogenic lineages was confirmed for both treatments. Cell activity was higher in the α-MEM/GL group than the DMEM/F12 group. PDT was calculated to be 60 h for the DMEM/F12 group, while for the α-MEM/GL group it was 47 h.
CONCLUSIONS: Our data reveal that α-MEM/GL with 10% FBS supports hUCM cell growth more strongly than DMEM/F12 with 10% FBS.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Effect of hypoxia on human adipose-derived mesenchymal stem cells and its potential clinical applications

Choi JR, Yong KW, Wan Safwani WKZ

Cell Mol Life Sci, 2017 07;74(14):2587-2600.
PMID: 28224204 DOI: 10.1007/s00018-017-2484-2

Human adipose-derived mesenchymal stem cells (hASCs) are an ideal cell source for regenerative medicine due to their capabilities of multipotency and the readily accessibility of adipose tissue. They have been found residing in a relatively low oxygen tension microenvironment in the body, but the physiological condition has been overlooked in most studies. In light of the escalating need for culturing hASCs under their physiological condition, this review summarizes the most recent advances in the hypoxia effect on hASCs. We first highlight the advantages of using hASCs in regenerative medicine and discuss the influence of hypoxia on the phenotype and functionality of hASCs in terms of viability, stemness, proliferation, differentiation, soluble factor secretion, and biosafety. We provide a glimpse of the possible cellular mechanism that involved under hypoxia and discuss the potential clinical applications. We then highlight the existing challenges and discuss the future perspective on the use of hypoxic-treated hASCs.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
The use of mesenchymal stromal cells in treatment of lung disorders

Kardia E, Zakaria N, Sarmiza Abdul Halim NS, Widera D, Yahaya BH

Regen Med, 2017 03;12(2):203-216.
PMID: 28244823 DOI: 10.2217/rme-2016-0112

The therapeutic use of mesenchymal stromal cells (MSCs) represents a promising alternative clinical strategy for treating acute and chronic lung disorders. Several preclinical reports demonstrated that MSCs can secrete multiple paracrine factors and that their immunomodulatory properties can support endothelial and epithelial regeneration, modulate the inflammatory cascade and protect lungs from damage. The effects of MSC transplantation into patients suffering from lung diseases should be fully evaluated through careful assessment of safety and associated risks, which is a prerequisite for translation of preclinical research into clinical practice. In this article, we summarize the current status of preclinical research and review initial MSC-based clinical trials for treating lung injuries and lung disorders.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
A Concise Review on Mesenchymal Stem Cells for Tissue Engineering with a Perspective on Ocular Surface Regeneration

Salih M, Shaharuddin B, Abdelrazeg S

Curr Stem Cell Res Ther, 2020;15(3):211-218.
PMID: 31995019 DOI: 10.2174/1574888X15666200129145251

Organ and tissue transplantation are limited by the scarcity of donated organs or tissue sources. The success of transplantation is limited by the risk of disease transmission and immunological- related rejection. There is a need for new strategies and innovative solutions to make transplantation readily available, safer and with less complications to increase the success rates. Accelerating progress in stem cell biology and biomaterials development have pushed tissue and organ engineering to a higher level. Among stem cells repertoire, Mesenchymal Stem Cells (MSC) are gaining interest and recognized as a cell population of choice. There is accumulating evidence that MSC growth factors, its soluble and insoluble proteins are involved in several key signaling pathways to promote tissue development, cellular differentiation and regeneration. MSC as multipotent non-hematopoietic cells with paracrine factors is advantageous for regenerative therapies. In this review, we discussed and summarized the important features of MSC including its immunomodulatory properties, mechanism of homing in the direction of tissue injury, licensing of MSC and the role of MSC soluble factors in cell-free therapy. Special consideration is highlighted on the rapidly growing research interest on the roles of MSC in ocular surface regeneration.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Fulltext Oxidative stress-induced premature senescence in Wharton's jelly-derived mesenchymal stem cells

Choo KB, Tai L, Hymavathee KS, Wong CY, Nguyen PN, Huang CJ, et al.

Int J Med Sci, 2014;11(11):1201-7.
PMID: 25249788 DOI: 10.7150/ijms.8356

On in vitro expansion for therapeutic purposes, the regenerative potentials of mesenchymal stem cells (MSCs) decline and rapidly enter pre-mature senescence probably involving oxidative stress. To develop strategies to prevent or slow down the decline of regenerative potentials in MSC culture, it is important to first address damages caused by oxidative stress-induced premature senescence (OSIPS). However, most existing OSIPS study models involve either long-term culture to achieve growth arrest or immediate growth arrest post oxidative agent treatment and are unsuitable for post-induction studies.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Fulltext Different isolation methods alter the gene expression profiling of adipose derived stem cells

Gnanasegaran N, Govindasamy V, Musa S, Kasim NH

Int J Med Sci, 2014;11(4):391-403.
PMID: 24669199 DOI: 10.7150/ijms.7697

Human adipose stem cells (ASCs) has been in the limelight since its discovery as a suitable source of mesenchymal stem cells (MSCs) in regenerative medicine. Currently, two major techniques are used to isolate ASCs, namely liposuction and tissue biopsy. These two methods are relatively risk-free but the question as to which method could give a more efficient output remains unclear. Thus, this study was carried out to compare and contrast the output generated in regards to growth kinetics, differentiation capabilities in vitro, and gene expression profiling. It was found that ASCs from both isolation methods were comparable in terms of growth kinetics and tri-lineage differentiation. Furthermore, ASCs from both populations were reported as CD44(+), CD73(+), CD90(+), CD166(+), CD34(-), CD45(-) and HLA-DR(-). However, in regards to gene expression, a group of overlapping genes as well as distinct genes were observed. Distinct gene expressions indicated that ASCs (liposuction) has endoderm lineage propensity whereas ASCs (biopsy) has a tendency towards mesoderm/ectoderm lineage. This information suggests involvement in different functional activity in accordance to isolation method. In conclusion, future studies to better understand these gene functions should be carried out in order to contribute in the applicability of each respective cells in regenerative therapy.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology
Fulltext Characterization of mononucleated human peripheral blood cells

Ab Kadir R, Zainal Ariffin SH, Megat Abdul Wahab R, Kermani S, Senafi S

ScientificWorldJournal, 2012;2012:843843.
PMID: 22666162 DOI: 10.1100/2012/843843

Unspecialized cells that can renew themselves and give rise to multiple differentiated cell types are termed stem cells. The objective of this study was to characterize and investigate, through molecular and biochemical analyses, the stemness of cells derived from isolated mononucleated cells that originated from peripheral blood. The isolated mononucleated cells were separated according to their physical characteristics (adherent and suspension), after 4 to 7 days into a 14-day culturing period in complete medium. Our results revealed that adherent and suspension cells were positive for mesenchymal stem cell (MSC) and hematopoietic stem cell (HSC) markers, respectively. Differentiation of adherent cells into osteoblasts was associated with expression of the OPN gene and increasing ALP enzyme activity, while differentiation of suspension cells into osteoclasts was associated with expression of the TRAP gene and increasing TRAP enzyme activity. In conclusion, molecular and biochemical analyses showed that mononucleated cells consist of MSC (adherent) and HSC (suspension), and both cell types are able to differentiate into specialized cells from their respective lineage: osteoblast (MSC) and osteoclast (HSC).

Matched MeSH terms: Mesenchymal Stromal Cells/cytology
Fulltext In-vitro differentiation study on isolated human mesenchymal stem cells

Mok PL, Cheong SK, Leong CF

Malays J Pathol, 2008 Jun;30(1):11-9.
PMID: 19108406 MyJurnal

Mesenchymal stem cells are pluripotent progenitors that could be found in human bone marrow. Mesenchymal stem cells are capable of renewing themselves without differentiation in long-term culture. These cells also have low immunogenicity and can suppress alloreactive T cell responses. In the current study, mesenchymal stem cells isolated and propagated previously from the bone marrow of a megaloblastic anaemia patient were tested for their capabilities to differentiate into adipocytes, chondrocytes and osteoblasts in vitro. The differentiated cells were determined by Oil Red O, Alcian Blue-PAS and Alizarin Red S staining, and reverse transcriptase-polymerase chain reaction to determine the expression of mRNA specific for adipogenesis, chondrogenesis and osteogenesis. The results showed that the fibroblast-like cells were capable of differentiating into adipocytes, chondrocytes and osteoblasts upon chemical induction. The adipocytes, chondrocytes and osteoblasts were stained positively to Oil Red O, Alcian Blue-PAS and Alizarin Red S respectively. The differentiated cells were also found to express mRNA specific for adipogenesis ('peroxisome proliferation-activated receptor gamma2' and lipoprotein lipase), chondrogenesis (collagen type II) and osteogenesis (osteocalcin, osteopontin and alkaline phosphatase). In conclusion, this research has successfully isolated fibroblast-like cells from human bone marrow and these cells demonstrated morphological, cytochemical and immunochemical characteristics similar to mesenchymal stem cells. These cells maintain their proliferative properties and could be differentiated into the mesoderm lineage. The success of this study is vital because mesenchymal stem cells can be used in cellular therapy to regenerate or replace damaged tissues, or as a vehicle for therapeutic gene delivery in the future.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Sourcing different neuro-progenitor cell for the use of nerve construct

Yazid AG, Anuar A, Onhmar HT, Ng AM, Ruszymah BH, Amaramalar SN

Med J Malaysia, 2008 Jul;63 Suppl A:113-4.
PMID: 19025011

Spinal cord, sciatic nerve, olfactory ensheathing cell and bone marrow derived mesenchymal stem cells were evaluated as an alternative source for tissue engineering of nerve conduit. All cell sources were cultured in alpha-MEM medium. Olfactory Ensheathing Cell (OEC) showed the best result with higher growth kinetic compared to the others. Spinal cord and sciatic nerve were positive for GFAP, OEC were positive for GFAP, S100b and anti-cytokeratin 18 but negative for anti-Human Fibroblast.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology
The effect of human mesenchymal stem cells on tumour cell proliferation

Sarmadi VH, Heng FS, Ramasamy R

Med J Malaysia, 2008 Jul;63 Suppl A:63-4.
PMID: 19024985

The therapeutic effect of mesenchymal stem cells (MSC) has been extensively investigated in recent decades, however this therapeutic effect has not been fully characterised. The aim of this study is to elucidate the inhibitory effect of MSC on haematopoietic tumour cells proliferation such as BV173 cell line. To this end, MSC generated from bone marrow, after immunophenotyping, they were co-cultured with tumour cell. The result shows that MSC profoundly inhibit the tumour cell proliferation via arresting the tumour cells at G0 and G1 phase of cell cycle.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Tissue-engineered bone via seeding bone marrow stem cell derived osteoblasts into coral: a rat model

Al-Salihi KA

Med J Malaysia, 2004 May;59 Suppl B:200-1.
PMID: 15468887

In the present study, natural coral of porites species was used as scaffold combined with in vitro expanded bone marrow stem cell derived osteoblasts (BMSC-DO), to develop a tissue-engineered bone graft in a rat model. Coral was molded into the shape of rat mandible seeded with 5x10(6) /ml BMSC-DO subsequently implanted subcutaneously in the back of 5 week Sprague dawely rats for 3 months. Coral alone was implanted as a control. The implants were harvest and processed for gross inspection and histological observations. The results showed that newly bone grafts were successfully formed coral seeded with cells group showed smooth highly vascularized like bone tissue. Histological sections revealed mature bone formation and lots of blood vessel, the bone formation occurred in the manner resemble intramembraneous bone formation. This study demonstrates that coral can be use as a suitable scaffold material for delivering bone marrow mesenchymal stem cells in tissue engineering.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Three dimensional alginate-fucoidan composite hydrogel augments the chondrogenic differentiation of mesenchymal stromal cells

Karunanithi P, Murali MR, Samuel S, Raghavendran HRB, Abbas AA, Kamarul T

Carbohydr Polym, 2016 08 20;147:294-303.
PMID: 27178935 DOI: 10.1016/j.carbpol.2016.03.102

Presence of sulfated polysaccharides like heparan sulphate has often been implicated in the regulation of chondrogenesis. However, recently there has been a plethora of interest in the use of non-animal extracted analogs of heparan sulphate. Here we remodeled alginate (1.5%) by incorporating fucoidan (0.5%), a natural sulphated polysaccharide extracted from seaweeds to form a composite hydrogel (Al-Fu), capable of enhancing chondrogenesis of human mesenchymal stromal cells (hMSCs). We confirmed the efficiency of fucoidan incorporation by FTIR and EDX analysis. Further, its ability to support hMSC attachment and chondrogenic differentiation was confirmed by SEM, biochemical glycosaminoglycan quantification, real-time quantitative PCR and immunocytochemical analyses of chondrogenic markers Sox-9, Collagen II, Aggrecan and COMP. Effect of Al-Fu hydrogel on hMSC hypertrophy was also confirmed by the downregulation of hypertrophic genes Collagen X and Runx2. This composite scaffold can hence be used as a cartilage biomimetic biomaterial to drive hMSC chondrogenesis and for other cartilage repair based therapies.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Cryopreservation of Human Mesenchymal Stem Cells for Clinical Applications: Current Methods and Challenges

Yong KW, Wan Safwani WK, Xu F, Wan Abas WA, Choi JR, Pingguan-Murphy B

Biopreserv Biobank, 2015 Aug;13(4):231-9.
PMID: 26280501 DOI: 10.1089/bio.2014.0104

Mesenchymal stem cells (MSCs) hold many advantages over embryonic stem cells (ESCs) and other somatic cells in clinical applications. MSCs are multipotent cells with strong immunosuppressive properties. They can be harvested from various locations in the human body (e.g., bone marrow and adipose tissues). Cryopreservation represents an efficient method for the preservation and pooling of MSCs, to obtain the cell counts required for clinical applications, such as cell-based therapies and regenerative medicine. Upon cryopreservation, it is important to preserve MSCs functional properties including immunomodulatory properties and multilineage differentiation ability. Further, a biosafety evaluation of cryopreserved MSCs is essential prior to their clinical applications. However, the existing cryopreservation methods for MSCs are associated with notable limitations, leading to a need for new or improved methods to be established for a more efficient application of cryopreserved MSCs in stem cell-based therapies. We review the important parameters for cryopreservation of MSCs and the existing cryopreservation methods for MSCs. Further, we also discuss the challenges to be addressed in order to preserve MSCs effectively for clinical applications.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
The effect of mesenchymal stem cell-secreted factors on airway epithelial repair

Halim NS, Aizat WM, Yahaya BH

Regen Med, 2019 01;14(1):15-31.
PMID: 30566028 DOI: 10.2217/rme-2018-0020

AIM: This study was aimed to investigate the effect of mesenchymal stem cell (MSC)-secreted factors on airway repair.
MATERIALS & METHODS: An indirect in vitro coculture model of injured airway epithelium explant with MSCs was developed. LC-MS/MS analysis was performed to determine factors secreted by MSCs and their involvement in epithelium repair was evaluated by histopathological assessment.
RESULTS: The identification of 54 of MSC proteins of which 44 of them were secretory/extracellular proteins. 43 of the secreted proteins were found to be involved in accelerating airway epithelium repair by stimulating the migratory, proliferative and differentiation abilities of the endogenous repair mechanisms. MSC-secreted proteins also initiated epithelial-mesenchymal transition process during early repair.
CONCLUSION: MSC-secreted factors accelerated airway epithelial repair by stimulating the endogenous reparative and regenerative ability of lung cells.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology
Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine

Gunawardena TNA, Rahman MT, Abdullah BJJ, Abu Kasim NH

J Tissue Eng Regen Med, 2019 04;13(4):569-586.
PMID: 30644175 DOI: 10.1002/term.2806

Recent studies suggest that the main driving force behind the therapeutic activity observed in mesenchymal stem cells (MSCs) are the paracrine factors secreted by these cells. These biomolecules also trigger antiapoptotic events to prevent further degeneration of the diseased organ through paracrine signalling mechanisms. In comparison with the normal physiological conditions, an increased paracrine gradient is observed within the peripheral system of diseased organs that enhances the migration of tissue-specific MSCs towards the site of infection or injury to promote healing. Thus, upon administration of conditioned media derived from mesenchymal stem cell cultures (MSC-CM) could contribute in maintaining the increased paracrine factor gradient between the diseased organ and the stem cell niche in order to speed up the process of recovery. Based on the principle of the paracrine signalling mechanism, MSC-CM, also referred as the secretome of the MSCs, is a rich source of the paracrine factors and are being studied extensively for a wide range of regenerative therapies such as myocardial infarction, stroke, bone regeneration, hair growth, and wound healing. This article highlights the current technological applications and advances of MSC-CM with the aim to appraise its future potential as a regenerative therapeutic agent.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Fulltext Isolation, characterization and the multi-lineage differentiation potential of rabbit bone marrow-derived mesenchymal stem cells

Tan SL, Ahmad TS, Selvaratnam L, Kamarul T

J Anat, 2013 Apr;222(4):437-50.
PMID: 23510053 DOI: 10.1111/joa.12032

Mesenchymal stem cells (MSCs) are recognized by their plastic adherent ability, fibroblastic-like appearance, expression of specific surface protein markers, and are defined by their ability to undergo multi-lineage differentiation. Although rabbit bone marrow-derived MSCs (rbMSCs) have been used extensively in previous studies especially in translational research, these cells have neither been defined morphologically and ultrastructurally, nor been compared with their counterparts in humans in their multi-lineage differentiation ability. A study was therefore conducted to define the morphology, surface marker proteins, ultrastructure and multi-lineage differentiation ability of rbMSCs. Herein, the primary rbMSC cultures of three adult New Zealand white rabbits (at least 4 months old) were used for three independent experiments. rbMSCs were isolated using the gradient-centrifugation method, an established technique for human MSCs (hMSCs) isolation. Cells were characterized by phase contrast microscopy observation, transmission electron microscopy analysis, reverse transcriptase-polymerase chain reaction (PCR) analysis, immunocytochemistry staining, flow cytometry, alamarBlue(®) assay, histological staining and quantitative (q)PCR analysis. The isolated plastic adherent cells were in fibroblastic spindle-shape and possessed eccentric, irregular-shaped nuclei as well as rich inner cytoplasmic zones similar to that of hMSCs. The rbMSCs expressed CD29, CD44, CD73, CD81, CD90 and CD166, but were negative (or dim positive) for CD34, CD45, CD117 and HLD-DR. Despite having similar morphology and phenotypic expression, rbMSCs possessed significantly larger cell size but had a lower proliferation rate as compared with hMSCs. Using established protocols to differentiate hMSCs, rbMSCs underwent osteogenic, adipogenic and chondrogenic differentiation. Interestingly, differentiated rbMSCs demonstrated higher levels of osteogenic (Runx2) and chondrogenic (Sox9) gene expressions than that of hMSCs (P 0.05). rbMSCs possess similar morphological characteristics to hMSCs, but have a higher potential for osteogenic and chondrogenic differentiation, despite having a lower cell proliferation rate than hMSCs. The characteristics reported here may be used as a comprehensive set of criteria to define or characterize rbMSCs.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology*
Adipose-Derived Mesenchymal Stem Cells Promote Growth and Migration of Lung Adenocarcinoma Cancer Cells

Zakaria N, Yahaya BH

Adv Exp Med Biol, 2020;1292:83-95.
PMID: 31916234 DOI: 10.1007/5584_2019_464

INTRODUCTION: Mesenchymal stem cells (MSCs) have been used in cancer therapy as vehicles to deliver therapeutic materials such as drugs, apoptosis inducers and cytokines due to their ability to migrate and home at the tumour site. Furthermore, MSCs have been genetically engineered to produce anticancer molecules such as TRAIL that can induce apoptosis of cancer cells. However, MSCs' presence in the tumour microenvironment has shown to be involved in promoting tumour growth and progression. Therefore, the roles of MSCs either promoting or suppressing tumorigenesis need to be investigated.
METHODS: Human adipose-derived MSCs (Ad-MSCs) and A549 cells are co-cultured together in indirect co-culture system using Transwell insert. Following co-culture, both cells were analysed in terms of growth rate, migration ability, apoptosis and gene expression for genes involved in migration and stemness characteristics.
RESULTS: The result shows that Ad-MSCs promoted the growth of A549 cells when indirectly co-cultured for 48 and 72 h. Furthermore, Ad-MSCs significantly enhanced the migration rate of A549 cells. The increased in migration rate was in parallel with the significant increase of MMP9. There are no significant changes observed in the expression of TWIST2, CDH2 and CDH1, genes involved in the epithelial-to-mesenchymal transition (EMT). Ad-MSCs also protect A549 cancer cells from undergoing apoptosis and increase the survival of cancer cells.
CONCLUSION: Secretion of soluble factors from Ad-MSCs has been shown to promote the growth and metastatic characteristics of A549 cancer cells. Therefore, the use of Ad-MSCs in cancer therapy needs to be carefully evaluated in the long-term aspect.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology

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