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Human umbilical cord-mesenchymal stem cells: a promising strategy for corneal epithelial regeneration

Azmi SM, Salih M, Abdelrazeg S, Roslan FF, Mohamed R, Tan JJ, et al.

Regen Med, 2020 03;15(3):1381-1397.
PMID: 32253974 DOI: 10.2217/rme-2019-0103

Aim: As a strategy to improve the outcome of ex vivo cultivated corneal epithelial transplantation, the role of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) is investigated in promoting corneal epithelial growth and functions. Materials & methods: Human telomerase-immortalized corneal epithelial cells were characterized and its functions evaluated by scratch migration assay, cellular senescence, HLA expression and spheres formation with hUC-MSC. Results: Expression of corneal epithelial markers was influenced by the duration and method of co-culture. Indirect co-culture improved cellular migration and delayed senescence when treated after 3 and 5 days. hUC-MSC downregulated expression of HLA Class I and II in IFN-γ-stimulated human telomerase-immortalized corneal epithelial cells. Conclusion: hUC-MSC promote corneal epithelial growth and functions after treatment with hUC-MSC.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
Fulltext Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of chronic obstructive pulmonary disease (COPD)

Ridzuan N, Zakaria N, Widera D, Sheard J, Morimoto M, Kiyokawa H, et al.

Stem Cell Res Ther, 2021 01 12;12(1):54.
PMID: 33436065 DOI: 10.1186/s13287-020-02088-6

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin.
METHODS: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student's t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD).
RESULTS: Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD.
CONCLUSIONS: In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Fulltext Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells

Chong PP, Selvaratnam L, Abbas AA, Kamarul T

J Orthop Res, 2012 Apr;30(4):634-42.
PMID: 21922534 DOI: 10.1002/jor.21556

The use of mesenchymal stem cells (MSCs) for cartilage repair has generated much interest owing to their multipotentiality. However, their significant presence in peripheral blood (PB) has been a matter of much debate. The objectives of this study are to isolate and characterize MSCs derived from PB and, compare their chondrogenic potential to MSC derived from bone marrow (BM). PB and BM derived MSCs from 20 patients were isolated and characterized. From 2 ml of PB and BM, 5.4 ± 0.6 million and 10.5 ± 0.8 million adherent cells, respectively, were obtained by cell cultures at passage 2. Both PB and BM derived MSCs were able to undergo tri-lineage differentiation and showed negative expression of CD34 and CD45, but positively expressed CD105, CD166, and CD29. Qualitative and quantitative examinations on the chondrogenic potential of PB and BM derived MSCs expressed similar cartilage specific gene (COMP) and proteoglycan levels, respectively. Furthermore, the s-GAG levels expressed by chondrogenic MSCs in cultures were similar to that of native chondrocytes. In conclusion, this study demonstrates that MSCs from PB maintain similar characteristics and have similar chondrogenic differentiation potential to those derived from BM, while producing comparable s-GAG expressions to chondrocytes.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Human mesenchymal stromal cells could deliver erythropoietin and migrate to the basal layer of hair shaft when subcutaneously implanted in a murine model

Mok PL, Cheong SK, Leong CF, Chua KH, Ainoon O

Tissue Cell, 2012 Aug;44(4):249-56.
PMID: 22560724 DOI: 10.1016/j.tice.2012.04.002

Mesenchymal stromal cells (MSC) are an attractive cell-targeting vehicle for gene delivery. MIDGE (an acronym for Minimalistic, Immunologically Defined Gene Expression) construct is relatively safer than the viral or plasmid expression system as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. The objective of this study was to test the ability of the human MSC (hMSC) to deliver the erythropoietin (EPO) gene in a nude mice model following nucleofection using a MIDGE construct. hMSC nucleofected with MIDGE encoding the EPO gene was injected subcutaneously in Matrigel at the dorsal flank of nude mice. Subcutaneous implantation of nucleofected hMSC resulted in increased hemoglobin level with presence of human EPO in the peripheral blood of the injected nude mice in the first two weeks post-implantation compared with the control groups. The basal layer of the hair shaft in the dermal layer was found to be significantly positive for immunohistochemical staining of a human EPO antibody. However, only a few basal layers of the hair shaft were found to be positively stained for CD105. In conclusion, hMSC harboring MIDGE-EPO could deliver and transiently express the EPO gene in the nude mice model. These cells could be localized to the hair follicle and secreted EPO protein might have possible role in hair regeneration.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Human bone marrow-derived mesenchymal stromal cells in combination with silymarin regulate hepatocyte growth factor expression and genotoxicity in carbon tetrachloride induced hepatotoxicity in Wistar rats

Aithal AP, Bairy LK, Seetharam RN, Rao MK

J Cell Biochem, 2019 08;120(8):13026-13036.
PMID: 30873677 DOI: 10.1002/jcb.28573

BACKGROUND: To evaluate the antimutagenic potential of combination treatment of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) and silymarin and its effect on hepatocyte growth factor levels in CCl4 induced hepatotoxicity in Wistar rats.
METHODS: Hepatotoxicity was induced in adult female Wistar rats using carbon tetrachloride (CCl4 ). Thirty-six rats were randomly divided into six groups with six rats in each group: Group 1 (normal control group), Group 2 (received only CCl 4 ), Group 3 (CCl 4 +low dose BM-MSCs), Group 4 (CCl 4 +high dose BM-MSCs), Group 5 (CCl 4 + silymarin), Group 6 (CCl 4 +silymarin+high dose BM-MSCs). Thirty days after the treatment, blood samples were collected for hepatocyte growth factor estimation. The rats were then killed, bone marrow was extracted for chromosomal aberration assay. Liver tissue was processed for evaluating the DNA fragmentation assay, histopathology, and scanning electron microscopy study.
RESULTS: Combination treatment of silymarin and high dose BM-MSCs significantly (P

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
Fulltext Generation and characterisation of human umbilical cord derived mesenchymal stem cells by explant method

Yusoff Z, Maqbool M, George E, Hassan R, Ramasamy R

Med J Malaysia, 2016 Jun;71(3):105-10.
PMID: 27495882 MyJurnal

Mesenchymal stem cells (MSCs) derived from human umbilical cord (UC) have been considered as an important tool for treating various malignancies, tissue repair and organ regeneration. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are better alternative to MSCs that derived from bone marrow (BM-MSCs) as they are regarded as medical waste with little ethical concern for research and easily culture-expanded. In this present study, the foetal distal end of human UC was utilised to generate MSC by explant method. Upon in vitro culture, adherent cells with fibroblastic morphology were generated with rapid growth kinetics. Under the respective inductive conditions, these cells were capable of differentiating into adipocytes and osteocytes; express an array of standard MSC's surface markers CD29, CD73, CD90, CD106 and MHC-class I. Further assessment of immunosuppression activity revealed that MSCs generated from UC had profoundly inhibited the proliferation of mitogen-activated T lymphocytes in a dosedependent manner. The current laboratory findings have reinforced the application of explant method to generate UCMSCs thus, exploring an ideal platform to fulfil the increasing demand of MSCs for research and potential clinical use.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation
Fulltext Fluoroscopy assisted minimally invasive transplantation of allogenic mesenchymal stromal cells embedded in HyStem reduces the progression of nucleus pulposus degeneration in the damaged ntervertebral [corrected] disc: a preliminary study in rabbits

Subhan RA, Puvanan K, Murali MR, Raghavendran HR, Shani S, Abdullah BJ, et al.

ScientificWorldJournal, 2014;2014:818502.
PMID: 24983002 DOI: 10.1155/2014/818502

This study was conducted to develop a technique for minimally invasive and accurate delivery of stem cells to augment nucleus pulposus (NP) in damaged intervertebral discs (IVD). IVD damage was created in noncontiguous discs at L4-L5 level; rabbits (N = 12) were randomly divided into three groups: group I treated with MSCs in HyStem hydrogel, group II treated with HyStem alone, and group III received no intervention. MSCs and hydrogel were administered to the damaged disc under guidance of fluoroscopy. Augmentation of NP was assessed through histological and MRI T2 mapping of the NP after eight weeks of transplantation. T2 weighted signal intensity was higher in group I than in groups II and III (P < 0.05). Disc height index showed maximum disc height in group I compared to groups II and III. Histological score of the degenerative index was significantly (P < 0.05) lower in group I (8.6 ± 1.8) than that in groups II (11.6 ± 2.3) and III (18.0 ± 5.7). Immunohistochemistry staining for collagen type II and aggrecan staining were higher in group I as compared to other groups. Our results demonstrate that the minimally invasive administration of MSCs in hyaluronan hydrogel (HyStem) augments the repair of NP in damaged IVD.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Fulltext Evaluation of locomotor function and microscopic structure of the spinal cord in a mouse model of experimental autoimmune encephalomyelitis following treatment with syngeneic mesenchymal stem cells

Mitra NK, Bindal U, Eng Hwa W, Chua CL, Tan CY

Int J Clin Exp Pathol, 2015;8(10):12041-52.
PMID: 26722389

Out of the minor myelin proteins, most significant one is myelin oligodendrocyte glycoprotein (MOG). Mesenchymal stem cells (MSCs) have proven immunoregulatory capacity. The objective of this study was to investigate the effects of syngeneic MSCs on mouse model of experimental autoimmune encephalomyelitis (EAE) through observation of locomotion by footprint analysis, histological analysis of spinal cord and estimation IL-17. C57BL/6 mice (10 weeks, n = 16) were immunized with 300 µg of MOG35-55 and 200 µL of complete Freund's adjuvant (CFA) to produce EAE model. Sham-treated control (n = 8) were injected with CFA. Half of immunized mice were given 100 µL of PBS (n = 8) and next half (n = 8) received 1 × 10(5) MSCs on day 11 through the tail veins. Clinical scoring showed development of EAE (loss of tonicity of tail and weakness of hind limb) on day 10. Following MSC treatment, clinical scores and hindlimb stride length showed significant improvement on day 15 onwards, compared to day 10 (P < 0.05). Under LFB staining, while PBS-treated group of EAE mice showed pale and degenerated axons in anterolateral white column of lumbar spinal cord, MSC-treated group showed numerous normal-looking axons. H&E staining showed normal axons in anterolateral white column and reduction of macrophages in MSC-treated EAE mice group. A lower level of IL-17 was observed in MSC treated EAE mice, compared to PBS-treated EAE mice. Our results suggest that Intravenous MSC has the potential to improve the locomotion and regeneration of axons in spinal cord in MOG-induced EAE model.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
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 Stem Cell Transplantation*
Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering

Choi JR, Yong KW, Choi JY

J Cell Physiol, 2018 Mar;233(3):1913-1928.
PMID: 28542924 DOI: 10.1002/jcp.26018

Today, articular cartilage damage is a major health problem, affecting people of all ages. The existing conventional articular cartilage repair techniques, such as autologous chondrocyte implantation (ACI), microfracture, and mosaicplasty, have many shortcomings which negatively affect their clinical outcomes. Therefore, it is essential to develop an alternative and efficient articular repair technique that can address those shortcomings. Cartilage tissue engineering, which aims to create a tissue-engineered cartilage derived from human mesenchymal stem cells (MSCs), shows great promise for improving articular cartilage defect therapy. However, the use of tissue-engineered cartilage for the clinical therapy of articular cartilage defect still remains challenging. Despite the importance of mechanical loading to create a functional cartilage has been well demonstrated, the specific type of mechanical loading and its optimal loading regime is still under investigation. This review summarizes the most recent advances in the effects of mechanical loading on human MSCs. First, the existing conventional articular repair techniques and their shortcomings are highlighted. The important parameters for the evaluation of the tissue-engineered cartilage, including chondrogenic and hypertrophic differentiation of human MSCs are briefly discussed. The influence of mechanical loading on human MSCs is subsequently reviewed and the possible mechanotransduction signaling is highlighted. The development of non-hypertrophic chondrogenesis in response to the changing mechanical microenvironment will aid in the establishment of a tissue-engineered cartilage for efficient articular cartilage repair.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
Effect of lawsone-preconditioned mesenchymal stem cells on the regeneration of pancreatic β cells in Type 1 diabetic rats

Masnoon J, Ishaque A, Khan I, Salim A, Kabir N

Cell Biochem Funct, 2023 Oct;41(7):833-844.
PMID: 37814478 DOI: 10.1002/cbf.3833

Diabetes is one of the major health issues globally. Type 1 diabetes mellitus develops due to the destruction of pancreatic β cells. Mesenchymal stem cells (MSCs) having remarkable self-renewal and differentiation potential, can regenerate β cells. MSCs preconditioned with bioactive small molecules possess enhanced biological features and therapeutic potential under in vivo environment. Interestingly, compounds of naphthoquinone class possess antidiabetic and anti-inflammatory properties, and can be explored as potential candidates for preconditioning MSCs. This study analyzed the effect of lawsone-preconditioned human umbilical cord MSCs (hUMSCs) on the regeneration of β cells in the streptozotocin (STZ)-induced Type 1 diabetes (T1D) rats. hUMSCs were isolated and characterized for the presence of surface markers. MSCs were preconditioned with optimized concentration of lawsone. T1D rat model was established by injecting 50 mg/kg of STZ intraperitoneally. Untreated and lawsone-preconditioned hUMSCs were transplanted into the diabetic rats via tail vein. Fasting blood sugar and body weight were monitored regularly for 4 weeks. Pancreas was harvested and β cell regeneration was evaluated by hematoxylin and eosin staining, and gene expression analysis. Immunohistochemistry was also done to assess the insulin expression. Lawsone-preconditioned hUMSCs showed better anti-hyperglycemic effect in comparison with untreated hUMSCs. Histological analysis presented the regeneration of islets of Langerhans with upregulated expression of βcell genes and reduced expression of inflammatory markers. Immunohistochemistry revealed strong insulin expression in the preconditioned hUMSCs compared with the untreated hUMSCs. It is concluded from the present study that lawsone-preconditioned hMSCs were able to exhibit pronounced anti-hyperglycemic effect in vivo compared with hUMSCs alone.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Dental pulp stem cells therapy overcome photoreceptor cell death and protects the retina in a rat model of sodium iodate-induced retinal degeneration

Alsaeedi HA, Koh AE, Lam C, Rashid MBA, Harun MHN, Saleh MFBM, et al.

J. Photochem. Photobiol. B, Biol., 2019 Sep;198:111561.
PMID: 31352000 DOI: 10.1016/j.jphotobiol.2019.111561

Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Cryopreserved mesenchymal stromal cell treatment is safe and feasible for severe dilated ischemic cardiomyopathy

Chin SP, Poey AC, Wong CY, Chang SK, Teh W, Mohr TJ, et al.

Cytotherapy, 2010;12(1):31-7.
PMID: 19878080 DOI: 10.3109/14653240903313966

Bone marrow (BM) mesenchymal stromal cells (MSC) represent a novel therapy for severe heart failure with extensive myocardial scarring, especially when performed concurrently with conventional revascularization. However, stem cells are difficult to transport in culture media without risk of contamination, infection and reduced viability. We tested the feasibility and safety of off-site MSC culture and expansion with freeze-controlled cryopreservation and subsequent rapid thawing of cells immediately prior to implantation to treat severe dilated ischemic cardiomyopathy.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
Cord blood-derived mesenchymal stem cell does not stimulate nor inhibits T lymphocytes activation

Tong CK, Seow HF, Ramasamy R

Med J Malaysia, 2008 Jul;63 Suppl A:77-8.
PMID: 19024992

The immune modulatory properties of mesenchymal stem cell (MSC) had brought a new insight in cell-based neotherapy. However, recent works of MSC are focused exclusively on bone marrow-derived MSC. We evaluated the immunogenicity of cord blood-derived MSC (CB-MSC) on T lymphocytes. Human peripheral blood mononuclear cells (PBMC) were prepared by density gradient separation and culture with the presence or absence of CB-MSC. PBMC were collected for activation analysis by flow cytometry at 24-, 48-, and 72- hours. The results showed that, CB-MSC does not stimulate nor inhibit T lymphocyte activation.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Comments on "Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model"

Gnanasegaran N

Cytotherapy, 2017 12;19(12):1551.
PMID: 29033284 DOI: 10.1016/j.jcyt.2017.09.002
Matched MeSH terms: Mesenchymal Stem Cell Transplantation
Collagen-coated polylactic-glycolic acid (PLGA) seeded with neural-differentiated human mesenchymal stem cells as a potential nerve conduit

Sulong AF, Hassan NH, Hwei NM, Lokanathan Y, Naicker AS, Abdullah S, et al.

Adv Clin Exp Med, 2014 May-Jun;23(3):353-62.
PMID: 24979505

Autologous nerve grafts to bridge nerve gaps pose various drawbacks. Nerve tissue engineering to promote nerve regeneration using artificial neural conduits has emerged as a promising alternative.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Characteristics and clinical applications of Wharton's jelly-derived mesenchymal stromal cells

Liau LL, Ruszymah BHI, Ng MH, Law JX

Curr Res Transl Med, 2020 01;68(1):5-16.
PMID: 31543433 DOI: 10.1016/j.retram.2019.09.001

Mesenchymal stromal cells (MSCs) are widely used in the clinic because they involve fewer ethical issues and safety concerns compared to other stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). MSCs derived from umbilical cord Wharton's jelly (WJ-MSCs) have excellent proliferative potential and a faster growth rate and can retain their multipotency for more passages in vitro compared to adult MSCs from bone marrow or adipose tissue. WJ-MSCs are used clinically for repairing tissue injuries of the spinal cord, liver and heart with the aim of regenerating tissue. On the other hand, WJ-MSCs are also used clinically to ameliorate immune-mediated diseases based on their ability to modulate immune responses. In the field of tissue engineering, WJ-MSCs capable of differentiating into multiple cell lineages have been used to produce a variety of engineered tissues in vitro that can then be transplanted in vivo. This review discusses the characteristics of WJ-MSCs, the differences between WJ-MSCs and adult MSCs, clinical studies involving WJ-MSCs and future perspectives of WJ-MSC research and clinical applications. To summarize, WJ-MSCs have shown promise in treating a variety of diseases clinically. However, most clinical trials/studies reported thus far are relatively smaller in scale. The collected evidence is insufficient to support the routine use of WJ-MSC therapy in the clinic. Thus, rigorous clinical trials are needed in the future to obtain more information on WJ-MSC therapy safety and efficacy.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
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 Stem Cell Transplantation*
Cell based therapy for osteoarthritis in a sheep model: gross and histological assessment

Alfaqeh H, Norhamdan MY, Chua KH, Chen HC, Aminuddin BS, Ruszymah BH

Med J Malaysia, 2008 Jul;63 Suppl A:37-8.
PMID: 19024972

This study was to determine if autologous bone marrow mesenchymal stem cells (BMSCs) cultured in chondrogenic medium could repair surgically induced osteoarthritis. Sheep BMSCs were cultured in medium containing 5ng/ml TGFbeta3 + 50ng/ml IGF-1 for three weeks. The cultured cells were then suspended at density of 2x10(6) cell/ml and injected intraarticularly into the osteoarthritic knee joint. After six weeks, the distal head of the femur and the proximal tibial plateau were removed and stained with H&E. The results indicated that knee joints treated with autologous BMSCs cultured in chondrogenic medium showed clear evidence of articular cartilage regeneration in comparison with other groups.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Biobanking of Human Mesenchymal Stem Cells: Future Strategy to Facilitate Clinical Applications

Yong KW, Choi JR, Wan Safwani WK

Adv Exp Med Biol, 2016;951:99-110.
PMID: 27837557

Human mesenchymal stem cells (hMSCs), a type of adult stem cells that hold great potential in clinical applications (e.g., regenerative medicine and cell-based therapy) due to their ability to differentiate into multiple types of specialized cells and secrete soluble factors which can initiate tissue repair and regulate immune response. hMSCs need to be expanded in vitro or cryopreserved to obtain sufficient cell numbers required for clinical applications. However, long-term in vitro culture-expanded hMSCs may raise some biosafety concerns (e.g., chromosomal abnormality and malignant transformation) and compromised functional properties, limiting their use in clinical applications. To avoid those adverse effects, it is essential to cryopreserve hMSCs at early passage and pool them for off-the-shelf use in clinical applications. However, the existing cryopreservation methods for hMSCs have some notable limitations. To address these limitations, several approaches have to be taken in order to produce healthy and efficacious cryopreserved hMSCs for clinical trials, which remains challenging to date. Therefore, a noteworthy amount of resources has been utilized in research in optimization of the cryopreservation methods, development of freezing devices, and formulation of cryopreservation media to ensure that hMSCs maintain their therapeutic characteristics without raising biosafety concerns following cryopreservation. Biobanking of hMSCs would be a crucial strategy to facilitate clinical applications in the future.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*

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