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Fulltext Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Ikram R, Shamsuddin SAA, Mohamed Jan B, Abdul Qadir M, Kenanakis G, Stylianakis MM, et al.

Molecules, 2022 Jan 07;27(2).
PMID: 35056690 DOI: 10.3390/molecules27020379

Thanks to stem cells' capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

Matched MeSH terms: Mesenchymal Stromal Cells*
Fulltext Mesenchymal stem cells: angels or demons?

Wong RS

J. Biomed. Biotechnol., 2011;2011:459510.
PMID: 21822372 DOI: 10.1155/2011/459510

Mesenchymal stem cells (MSCs) have been used in cell-based therapy in various disease conditions such as graft-versus-host and heart diseases, osteogenesis imperfecta, and spinal cord injuries, and the results have been encouraging. However, as MSC therapy gains popularity among practitioners and researchers, there have been reports on the adverse effects of MSCs especially in the context of tumour modulation and malignant transformation. These cells have been found to enhance tumour growth and metastasis in some studies and have been related to anticancer-drug resistance in other instances. In addition, various studies have also reported spontaneous malignant transformation of MSCs. The mechanism of the modulatory behaviour and the tumorigenic potential of MSCs, warrant urgent exploration, and the use of MSCs in patients with cancer awaits further evaluation. However, if MSCs truly play a role in tumour modulation, they can also be potential targets of cancer treatment.

Matched MeSH terms: Mesenchymal Stromal Cells*
Role of circular RNAs in determining the fate of mesenchymal stem cells

Wong RSY, Cheong SK

Malays J Pathol, 2021 Aug;43(2):241-250.
PMID: 34448788

Ribonucleic acid (RNA) has been well-understood for its linear form for many years. With advances in high-throughput sequencing, there is an increasing focus on circular RNAs (circRNAs) recently. Although they were previously regarded as splicing error by-products, research has shown that they play a pivotal role in many cellular processes, one of which is the control of stem cell differentiation and fate. On the other hand, decades of research have demonstrated the promising therapeutic potential of mesenchymal stem cells (MSCs). To this end, there is a growing body of research on the role of circRNAs in the determination of the fate of MSCs. This review critically examines the current evidence and consolidates key findings from studies that explore the involvement of circRNAs in the regulation of MSC differentiation.

Matched MeSH terms: Mesenchymal Stromal Cells*
Fulltext Empowering Mesenchymal Stem Cells for Ocular Degenerative Disorders

Ding SSL, Subbiah SK, Khan MSA, Farhana A, Mok PL

Int J Mol Sci, 2019 Apr 10;20(7).
PMID: 30974904 DOI: 10.3390/ijms20071784

Multipotent mesenchymal stem cells (MSCs) have been employed in numerous pre-clinical and clinical settings for various diseases. MSCs have been used in treating degenerative disorders pertaining to the eye, for example, age-related macular degeneration, glaucoma, retinitis pigmentosa, diabetic retinopathy, and optic neuritis. Despite the known therapeutic role and mechanisms of MSCs, low cell precision towards the targeted area and cell survivability at tissue needing repair often resulted in a disparity in therapeutic outcomes. In this review, we will discuss the current and feasible strategy options to enhance treatment outcomes with MSC therapy. We will review the application of various types of biomaterials and advances in nanotechnology, which have been employed on MSCs to augment cellular function and differentiation for improving treatment of visual functions. In addition, several modes of gene delivery into MSCs and the types of associated therapeutic genes that are important for modulation of ocular tissue function and repair will be highlighted.

Matched MeSH terms: Mesenchymal Stromal Cells/metabolism*; Mesenchymal Stromal Cells/pathology
Mesenchymal stromal cell-like characteristics of corneal keratocytes

Choong PF, Mok PL, Cheong SK, Then KY

Cytotherapy, 2007;9(3):252-8.
PMID: 17464757

The unique potential of mesenchymal stromal cells (MSC) has generated much research interest recently, particularly in exploring the regenerative nature of these cells. Previously, MSC were thought to be found only in the BM. However, further studies have shown that MSC can also be isolated from umbilical cord blood, adipose tissue and amniotic fluid. In this study, we explored the possibility of MSC residing in the cornea.

Matched MeSH terms: Stromal Cells*; Mesenchymal Stromal Cells*
Fulltext Mesenchymal stromal cells for cartilage repair in osteoarthritis

Mamidi MK, Das AK, Zakaria Z, Bhonde R

Osteoarthritis Cartilage, 2016 Aug;24(8):1307-16.
PMID: 26973328 DOI: 10.1016/j.joca.2016.03.003

Treatment for articular cartilage damage is quite challenging as it shows limited repair and regeneration following injury. Non-operative and classical surgical techniques are inefficient in restoring normal anatomy and function of cartilage in osteoarthritis (OA). Thus, investigating new and effective strategies for OA are necessary to establish feasible therapeutic solutions. The emergence of the new discipline of regenerative medicine, having cell-based therapy as its primary focus, may enable us to achieve repair and restore the damaged articular cartilage. This review describes progress and development of employing mesenchymal stromal cell (MSC)-based therapy as a promising alternative for OA treatment. The objective of this review is to first, discuss how in vitro MSC chondrogenic differentiation mimics in vivo embryonic cartilage development, secondly, to describe various chondrogenic differentiation strategies followed by pre-clinical and clinical studies demonstrating their feasibility and efficacy. However, several challenges need to be tackled before this research can be translated to the clinics. In particular, better understanding of the post-transplanted cell behaviour and learning to enhance their potency in the disease microenvironment is essential. Final objective is to underscore the importance of isolation, storage, cell shipment, route of administration, optimum dosage and control batch to batch variations to realise the full potential of MSCs in OA clinical trials.

Matched MeSH terms: Mesenchymal Stromal Cells*
Response to: 'Umbilical-cord messenchymal stem cells for the treatment of automimmune diseases: beware of cell to cell contact' by Alunno et al

Lim TO, Deng D, Zhang P, Guo Y

Ann Rheum Dis, 2018 03;77(3):e15.
PMID: 28663307 DOI: 10.1136/annrheumdis-2017-211808
Matched MeSH terms: Mesenchymal Stromal Cells*
Senotherapeutics for mesenchymal stem cell senescence and rejuvenation

Wong PF, Dharmani M, Ramasamy TS

Drug Discov Today, 2023 Jan;28(1):103424.
PMID: 36332835 DOI: 10.1016/j.drudis.2022.103424

Mesenchymal stem cells (MSCs) are susceptible to replicative senescence and senescence-associated functional decline, which hampers their use in regenerative medicine. Senotherapeutics are drugs that target cellular senescence through senolytic and senomorphic functions to induce apoptosis and suppress chronic inflammation caused by the senescence-associated secreted phenotype (SASP), respectively. Therefore, senotherapeutics could delay aging-associated degeneration. They could also be used to eliminate senescent MSCs during in vitro expansion or bioprocessing for transplantation. In this review, we discuss the role of senotherapeutics in MSC senescence, rejuvenation, and transplantation, with examples of some tested compounds in vitro. The prospects, challenges, and the way forward in clinical applications of senotherapeutics in cell-based therapeutics are also discussed.

Matched MeSH terms: Mesenchymal Stromal Cells*
Mesenchymal Stromal Cells-Derived Exosome and the Roles in the Treatment of Traumatic Brain Injury

Mot YY, Moses EJ, Mohd Yusoff N, Ling KH, Yong YK, Tan JJ

Cell Mol Neurobiol, 2023 Mar;43(2):469-489.
PMID: 35103872 DOI: 10.1007/s10571-022-01201-y

Traumatic brain injury (TBI) could result in life-long disabilities and death. Though the mechanical insult causes primary injury, the secondary injury due to dysregulated responses following neuronal apoptosis and inflammation is often the cause for more detrimental consequences. Mesenchymal stromal cell (MSC) has been extensively investigated as the emerging therapeutic for TBI, and the functional properties are chiefly attributed to their secretome, especially the exosomes. Delivering these nanosize exosomes have shown to ameliorate post-traumatic injury and restore brain functions. Recent technology advances also allow engineering MSC-derived exosomes to carry specific biomolecules of interest to augment their therapeutic outcome. In this review, we discuss the pathophysiology of TBI and summarize the recent progress in the applications of MSCs-derived exosomes, the roles and the signalling mechanisms underlying the protective effects in the treatment of the TBI.

Matched MeSH terms: Mesenchymal Stromal Cells*
Bone marrow-derived mesenchymal stem cells: A promising therapeutic option for the treatment of diabetic foot ulcers

Dama G, Du J, Zhu X, Liu Y, Lin J

Diabetes Res Clin Pract, 2023 Jan;195:110201.
PMID: 36493913 DOI: 10.1016/j.diabres.2022.110201

Chronic wounds fail to heal through the three normal stages of healing (inflammatory, proliferative, and remodelling), resulting in a chronic tissue injury that is not repaired within the average time limit. Patients suffering from type 1 and type 2 diabetes are prone to develop diabetic foot ulcers (DFUs), which commonly develop into chronic wounds that are non treatable with conventional therapies. DFU develops due to various risk factors, such as peripheral neuropathy, peripheral vascular disease, arterial insufficiency, foot deformities, trauma and impaired resistance to infection. DFUs have gradually become a major problem in the health care system worldwide. In this review, we not only focus on the pathogenesis of DFU but also comprehensively summarize the outcomes of preclinical and clinical studies thus far and the potential therapeutic mechanism of bone marrow-derived mesenchymal stem cells (BMSCs) for the treatment of DFU. Based on the published results, BMSC transplantation can contribute to wound healing through growth factor secretion, anti-inflammation, differentiation into tissue-specific cells, neovascularization, re-epithelialization and angiogenesis in DFUs. Moreover, clinical trials showed that BMSC treatment in patients with diabetic ulcers improved ulcer healing and the ankle-brachial index, ameliorated pain scores, and enhanced claudication walking distances with no reported complications. In conclusion, although BMSC transplantation exhibits promising therapeutic potential in DFU treatment, additional studies should be performed to confirm their efficacy and long-term safety in DFU patients.

Matched MeSH terms: Mesenchymal Stromal Cells*
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; Mesenchymal Stromal Cells/secretion*
Fulltext Mesenchymal stem cells inhibit proliferation of lymphoid origin haematopoietic tumour cells by inducing cell cycle arrest

Sarmadi VH, Tong CK, Vidyadaran S, Abdullah M, Seow HF, Ramasamy R

Med J Malaysia, 2010 Sep;65(3):209-14.
PMID: 21939170

We have previously shown that mesenchymal stem cells (MSC) inhibit tumour cell proliferation, thus promising a novel therapy for treating cancers. In this study, MSC were generated from human bone marrow samples and characterised based on standard immunophenotyping. When MSC were co-cultured with BV173 and Jurkat tumour cells, the proliferation of tumour cells were profoundly inhibited in a dose dependent manner mainly via cell to cell contact interaction. Further cell cycle analysis reveals that MSC arrest tumour cell proliferation in G0/G1 phase of cell cycle thus preventing the entry of tumour cells into S phase of cell cycle.

Matched MeSH terms: Mesenchymal Stromal Cells/metabolism; Mesenchymal Stromal Cells/physiology*
Fulltext Cellular mechanisms of emerging applications of mesenchymal stem cells

Mok PL, Leong CF, Cheong SK

Malays J Pathol, 2013 Jun;35(1):17-32.
PMID: 23817392 MyJurnal

Mesenchymal stem cells (MSC) are multipotent, self-renewing cells that can be found mainly in the bone marrow, and other post-natal organs and tissues. The ease of isolation and expansion, together with the immunomodulatory properties and their capability to migrate to sites of inflammation and tumours make them a suitable candidate for therapeutic use in the clinical settings. We review here the cellular mechanisms underlying the emerging applications of MSC in various fields.

Matched MeSH terms: Mesenchymal Stromal Cells/physiology*
Fulltext Potential of Exosomes as Cell-Free Therapy in Articular Cartilage Regeneration: A Review

Ng CY, Chai JY, Foo JB, Mohamad Yahaya NH, Yang Y, Ng MH, et al.

Int J Nanomedicine, 2021;16:6749-6781.
PMID: 34621125 DOI: 10.2147/IJN.S327059

Treatment of cartilage defects such as osteoarthritis (OA) and osteochondral defect (OCD) remains a huge clinical challenge in orthopedics. OA is one of the most common chronic health conditions and is mainly characterized by the degeneration of articular cartilage, shown in the limited capacity for intrinsic repair. OCD refers to the focal defects affecting cartilage and the underlying bone. The current OA and OCD management modalities focus on symptom control and on improving joint functionality and the patient's quality of life. Cell-based therapy has been evaluated for managing OA and OCD, and its chondroprotective efficacy is recognized mainly through paracrine action. Hence, there is growing interest in exploiting extracellular vesicles to induce cartilage regeneration. In this review, we explore the in vivo evidence of exosomes on cartilage regeneration. A total of 29 in vivo studies from the PubMed and Scopus databases were identified and analyzed. The studies reported promising results in terms of in vivo exosome delivery and uptake; improved cartilage morphological, histological, and biochemical outcomes; enhanced subchondral bone regeneration; and improved pain behavior following exosome treatment. In addition, exosome therapy is safe, as the included studies documented no significant complications. Modifying exosomal cargos further increased the cartilage and subchondral bone regeneration capacity of exosomes. We conclude that exosome administration is a potent cell-free therapy for alleviating OA and OCD. However, additional studies are needed to confirm the therapeutic potential of exosomes and to identify the standard protocol for exosome-based therapy in OA and OCD management.

Matched MeSH terms: Mesenchymal Stromal Cells*
Therapeutic potential of human umbilical cord-derived mesenchymal stem cells transplantation in rats with optic nerve injury

Looi SY, Bastion MC, Leow SN, Luu CD, Hairul NMH, Ruhaslizan R, et al.

Indian J Ophthalmol, 2022 Jan;70(1):201-209.
PMID: 34937239 DOI: 10.4103/ijo.IJO_473_21

Purpose: There are no effective treatments currently available for optic nerve transection injuries. Stem cell therapy represents a feasible future treatment option. This study investigated the therapeutic potential of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation in rats with optic nerve injury.
Methods: Sprague-Dawley (SD) rats were divided into three groups: a no-treatment control group (n = 6), balanced salt solution (BSS) treatment group (n = 6), and hUC-MSCs treatment group (n = 6). Visual functions were assessed by flash visual evoked potential (fVEP) at baseline, Week 3, and Week 6 after optic nerve crush injury. Right eyes were enucleated after 6 weeks for histology.
Results: The fVEP showed shortened latency delay and increased amplitude in the hUC-MSCs treated group compared with control and BSS groups. Higher cellular density was detected in the hUC-MSC treated group compared with the BSS and control groups. Co-localized expression of STEM 121 and anti-S100B antibody was observed in areas of higher nuclear density, both in the central and peripheral regions.
Conclusion: Peribulbar transplantation of hUC-MSCs demonstrated cellular integration that can potentially preserve the optic nerve function with a significant shorter latency delay in fVEP and higher nuclear density on histology, and immunohistochemical studies observed cell migration particularly to the peripheral regions of the optic nerve.

Matched MeSH terms: Mesenchymal Stromal Cells*
Fulltext Human Mesenchymal Stem Cell-Derived Miniature Joint System for Disease Modeling and Drug Testing

Li Z, Lin Z, Liu S, Yagi H, Zhang X, Yocum L, et al.

Adv Sci (Weinh), 2022 Jul;9(21):e2105909.
PMID: 35436042 DOI: 10.1002/advs.202105909

Diseases of the knee joint such as osteoarthritis (OA) affect all joint elements. An in vitro human cell-derived microphysiological system capable of simulating intraarticular tissue crosstalk is desirable for studying etiologies/pathogenesis of joint diseases and testing potential therapeutics. Herein, a human mesenchymal stem cell-derived miniature joint system (miniJoint) is generated, in which engineered osteochondral complex, synovial-like fibrous tissue, and adipose tissue are integrated into a microfluidics-enabled bioreactor. This novel design facilitates different tissues communicating while still maintaining their respective phenotypes. The miniJoint exhibits physiologically relevant changes when exposed to interleukin-1β mediated inflammation, which are similar to observations in joint diseases in humans. The potential of the miniJoint in predicting in vivo efficacy of drug treatment is confirmed by testing the "therapeutic effect" of the nonsteroidal anti-inflammatory drug, naproxen, as well as four other potential disease-modifying OA drugs. The data demonstrate that the miniJoint recapitulates complex tissue interactions, thus providing a robust organ chip model for the study of joint pathology and the development of novel therapeutic interventions.

Matched MeSH terms: Mesenchymal Stromal Cells*
Fulltext Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

Kou M, Huang L, Yang J, Chiang Z, Chen S, Liu J, et al.

Cell Death Dis, 2022 Jul 04;13(7):580.
PMID: 35787632 DOI: 10.1038/s41419-022-05034-x

Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.

Matched MeSH terms: Mesenchymal Stromal Cells*
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*; Mesenchymal Stromal Cells/physiology; Mesenchymal Stromal Cells/ultrastructure
Fulltext Enhancement of mesenchymal stem cell chondrogenesis with short-term low intensity pulsed electromagnetic fields

Parate D, Franco-Obregón A, Fröhlich J, Beyer C, Abbas AA, Kamarul T, et al.

Sci Rep, 2017 08 25;7(1):9421.
PMID: 28842627 DOI: 10.1038/s41598-017-09892-w

Pulse electromagnetic fields (PEMFs) have been shown to recruit calcium-signaling cascades common to chondrogenesis. Here we document the effects of specified PEMF parameters over mesenchymal stem cells (MSC) chondrogenic differentiation. MSCs undergoing chondrogenesis are preferentially responsive to an electromagnetic efficacy window defined by field amplitude, duration and frequency of exposure. Contrary to conventional practice of administering prolonged and repetitive exposures to PEMFs, optimal chondrogenic outcome is achieved in response to brief (10 minutes), low intensity (2 mT) exposure to 6 ms bursts of magnetic pulses, at 15 Hz, administered only once at the onset of chondrogenic induction. By contrast, repeated exposures diminished chondrogenic outcome and could be attributed to calcium entry after the initial induction. Transient receptor potential (TRP) channels appear to mediate these aspects of PEMF stimulation, serving as a conduit for extracellular calcium. Preventing calcium entry during the repeated PEMF exposure with the co-administration of EGTA or TRP channel antagonists precluded the inhibition of differentiation. This study highlights the intricacies of calcium homeostasis during early chondrogenesis and the constraints that are placed on PEMF-based therapeutic strategies aimed at promoting MSC chondrogenesis. The demonstrated efficacy of our optimized PEMF regimens has clear clinical implications for future regenerative strategies for cartilage.

Matched MeSH terms: Mesenchymal Stromal Cells/cytology; Mesenchymal Stromal Cells/metabolism*; Mesenchymal Stromal Cells/radiation effects*
Fulltext Platelet rich concentrate promotes early cellular proliferation and multiple lineage differentiation of human mesenchymal stromal cells in vitro

Shani S, Ahmad RE, Naveen SV, Murali MR, Puvanan K, Abbas AA, et al.

ScientificWorldJournal, 2014;2014:845293.
PMID: 25436230 DOI: 10.1155/2014/845293

Platelet rich concentrate (PRC) is a natural adjuvant that aids in human mesenchymal stromal cell (hMSC) proliferation in vitro; however, its role requires further exploration. This study was conducted to determine the optimal concentration of PRC required for achieving the maximal proliferation, and the need for activating the platelets to achieve this effect, and if PRC could independently induce early differentiation of hMSC. The gene expression of markers for osteocytes (ALP, RUNX2), chondrocytes (SOX9, COL2A1), and adipocytes (PPAR-γ) was determined at each time point in hMSC treated with 15% activated and nonactivated PRC since maximal proliferative effect was achieved at this concentration. The isolated PRC had approximately fourfold higher platelet count than whole blood. There was no significant difference in hMSC proliferation between the activated and nonactivated PRC. Only RUNX2 and SOX9 genes were upregulated throughout the 8 days. However, protein expression study showed formation of oil globules from day 4, significant increase in ALP at days 6 and 8 (P ≤ 0.05), and increased glycosaminoglycan levels at all time points (P < 0.05), suggesting the early differentiation of hMSC into osteogenic and adipogenic lineages. This study demonstrates that the use of PRC increased hMSC proliferation and induced early differentiation of hMSC into multiple mesenchymal lineages, without preactivation or addition of differentiation medium.

Matched MeSH terms: Mesenchymal Stromal Cells/physiology*

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