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Towards engineering of a tracheal equivalent: identification of epithelial precursor cells, differentiation and cocultivation techniques

Rotter N, Stölzel K, Endres M, Leinhase I, Ziegelaar BW, Sittinger M

Med J Malaysia, 2004 May;59 Suppl B:35-6.
PMID: 15468806
Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Tissue engineering techniques in tendon and ligament replacement

Goh JC, Ouyang HW, Toh SL, Lee EH

Med J Malaysia, 2004 May;59 Suppl B:47-8.
PMID: 15468812
Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Fulltext Neural-differentiated mesenchymal stem cells incorporated into muscle stuffed vein scaffold forms a stable living nerve conduit

Hassan NH, Sulong AF, Ng MH, Htwe O, Idrus RB, Roohi S, et al.

J Orthop Res, 2012 Oct;30(10):1674-81.
PMID: 22411691 DOI: 10.1002/jor.22102

Autologous nerve grafts to bridge nerve gaps have donor site morbidity and possible neuroma formation resulting in development of various methods of bridging nerve gaps without using autologous nerve grafts. We have fabricated an acellular muscle stuffed vein seeded with differentiated mesenchymal stem cells (MSCs) as a substitute for nerve autografts. Human vein and muscle were both decellularized by liquid nitrogen immersion with subsequent hydrolysis in hydrochloric acid. Human MSCs were subjected to a series of treatments with a reducing agent, retinoic acid, and a combination of trophic factors. The differentiated MSCs were seeded on the surface of acellular muscle tissue and then stuffed into the vein. Our study showed that 35-75% of the cells expressed neural markers such as S100b, glial fibrillary acidic protein (GFAP), p75 NGF receptor, and Nestin after differentiation. Histological and ultra structural analyses of muscle stuffed veins showed attachment of cells onto the surface of the acellular muscle and penetration of the cells into the hydrolyzed fraction of muscle fibers. We implanted these muscle stuffed veins into athymic mice and at 8 weeks post-implantation, the acellular muscle tissue had fully degraded and replaced with new matrix produced by the seeded cells. The vein was still intact and no inflammatory reactions were observed proving the biocompatibility and biodegradability of the conduit. In conclusion, we have successfully formed a stable living nerve conduit which may serve as a substitute for autologous nerves.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
Mesenchymal stem cells: From stem cells to sarcomas

Lye KL, Nordin N, Vidyadaran S, Thilakavathy K

Cell Biol Int, 2016 Jun;40(6):610-8.
PMID: 26992453 DOI: 10.1002/cbin.10603

Mesenchymal stem cells (MSCs) have garnered vast interests in clinical settings, especially in regenerative medicine due to their unique properties-they are reliably isolated and expanded from various tissue sources; they are able to differentiate into mesodermal tissues such as bones, cartilages, adipose tissues, and muscles; and they have unique immunosuppressive properties. However, there are some concerns pertaining to the role of MSCs in the human body. On one hand, they are crucial component in the regeneration and repair of the human body. On the contrary, they are shown to transform into sarcomas. Although the exact mechanisms are still unknown, many new leads have pointed to the belief that MSCs do play a role in sarcomagenesis. This review focuses on the current updates and findings of the role of MSCs in their transformation process into sarcomas.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods
Fulltext Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review

Teh SW, Mok PL, Abd Rashid M, Bastion MC, Ibrahim N, Higuchi A, et al.

Int J Mol Sci, 2018 Feb 13;19(2).
PMID: 29438279 DOI: 10.3390/ijms19020558

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

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*
Histological characterization of pulp regeneration using decellularized human dental pulp and mesenchymal stem cells in a feline model

Tan YY, Abdullah D, Abu Kasim NH, Yazid F, Mahamad Apandi NI, Ramanathan A, et al.

Tissue Cell, 2024 Oct;90:102484.
PMID: 39068688 DOI: 10.1016/j.tice.2024.102484

Regenerative endodontics aims to restore pulp tissues, thus preserving the vitality of the tooth. One promising approach involves the utilization of decellularized human dental pulp (DHDP) as a scaffold repopulated with Wharton's Jelly mesenchymal stem cells (WJMSCs). This study aimed to regenerate pulp tissues using DHDP and WJMSCs following pulpectomy in mature canine teeth of a feline animal model and to investigate the histological features of the regenerated pulp. A 12-month-old male domestic shorthaired felines were used as subjects. Teeth were categorized into untreated (Group 1), pulpectomy with mineral trioxide aggregate (MTA) (Group 2), and pulpectomy with DHDP-repopulated scaffold and MTA (Group 3). The animals were sacrificed six weeks post-intervention. H&E and immunohistochemistry using anti-collagen type 1 and laminin antibodies were used to stain the tissue sections. Histological examinations presented pulp-like tissues in Group 3, with tissue components similar to the structures found in Group 1. Immunohistochemical analysis demonstrated the presence of collagen type I and laminin within the regenerated tissues. The root canals of teeth in Group 2 were devoid of pulpal tissue. DHDP with WJMSCs can potentially be used for pulp regeneration, supporting the modality for developing new clinical protocols in stem cell therapy.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation
Treatment outcomes of alginate-embedded allogenic mesenchymal stem cells versus autologous chondrocytes for the repair of focal articular cartilage defects in a rabbit model

Tay LX, Ahmad RE, Dashtdar H, Tay KW, Masjuddin T, Ab-Rahim S, et al.

Am J Sports Med, 2012 Jan;40(1):83-90.
PMID: 21917609 DOI: 10.1177/0363546511420819

Mesenchymal stem cells (MSCs) represent a promising alternative form of cell-based therapy for cartilage injury. However, the capacity of MSCs for chondrogenesis has not been fully explored. In particular, there is presently a lack of studies comparing the effectiveness of MSCs to conventional autologous chondrocyte (autoC) treatment for regeneration of full-thickness cartilage defects in vivo.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
Treat the graft to improve the regenerative ability of the host

Mamidi MK, Pal R, Govindasamy V, Zakaria Z, Bhonde R

Med Hypotheses, 2011 Apr;76(4):599-601.
PMID: 21277690 DOI: 10.1016/j.mehy.2011.01.010

The staggering number of publications featuring the use of stem cells has revolutionized regenerative medicine research. Preclinical studies indicate that allogeneic human mesenchymal stem cells (MSCs) may be useful for the treatment of several clinical disorders, including sepsis, acute renal failure, acute myocardial infarction, and more recently, acute lung injury (ALI). However, considerable success would not be obtained in clinical trials due to poor survival of transplanted cells under the influence of inflammatory conditions. Despite robust approaches like cellular reprogramming, scaffolds and conditioned media have been tested to overcome this problem; however the success rate of these approaches remain questionable. Recently, pretreatment of bioactive compounds in vitro have been shown to suppress cell apoptosis and promote cell survival. Quite likely a similar phenomenon can take place in vivo. Based on such studies, we hypothesize that MSCs derived from human post-natal tissues could be conditioned and prepared for targeted disease therapy. Depending on the disease condition, the MSCs could be treated prior to delivery with appropriate bioactive compounds to allow them survive longer and perform a better role as biocatalyst. The advantage of this approach could be the tailor made availability of MSCs preconditioned with appropriate bioactive compounds for disease specific therapy. Therefore, the choice of suitable bioactive molecule is likely to enhance the efficacy of targeted stem cell therapy and preconditioning may provide a novel strategy in maximizing biological and functional properties of MSCs.

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*
Approaches to deriving Schwann cells from human bone marrow for neural tube regeneration in a clinical setting

Hidayah HN, Mazzre M, Ng AM, Ruszymah BH, Shalimar A

Med J Malaysia, 2008 Jul;63 Suppl A:39-40.
PMID: 19024973

Bone marrow derived Mesenchymal stem cells (MSCs) were evaluated as an alternative source for tissue engineering of peripheral nerves. Human MSCs were subjected to a series of treatment with a reducing agent, retinoic acid and a combination of trophic factors. This treated MSCs differentiated into Schwann cells were characterized in vitro via flow cytometry analysis and immunocytochemically. In contrast to untreated MSCs, differentiated MSCs expressed Schwann cell markers in vitro, as we confirmed by flow cytometry analysis and immunocytochemically. These results suggest that human MSCs can be induced to be a substitute for Schwann cells that may be applied for nerve regeneration since it is difficult to grow Schwann cells in vitro.

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*
Tissue-engineered bone applied for alveolar ridge augmentation with simultaneous implant

Ueda M

Med J Malaysia, 2004 May;59 Suppl B:29.
PMID: 15468803
Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Using tissue engineering techniques for osteochondral repair and regeneration

Goh JC, Shao XX, Hutmacher D, Lee EH

Med J Malaysia, 2004 May;59 Suppl B:17-8.
PMID: 15468797
Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
Neurogenic plasticity of mesenchymal stem cell, an alluring cellular replacement for traumatic brain injury

Pati S, Muthuraju S, Hadi RA, Huat TJ, Singh S, Maletic-Savatic M, et al.

Curr Stem Cell Res Ther, 2016;11(2):149-57.
PMID: 26763886

Traumatic brain injury (TBI) imposes horrendous neurophysiological alterations leading to most devastating forms of neuro-disability. Which includes impaired cognition, distorted locomotors activity and psychosomatic disability in both youths and adults. Emerging evidence from recent studies has identified mesenchymal stem cells (MSCs) as one of the promising category of stem cells having excellent neuroregenerative capability in TBI victims. Some of the clinical and animal studies reported that MSCs transplantation could cure neuronal damage as well as improve cognitive and locomotors behaviors in TBI. However, mechanism behind their broad spectrum neuroregenerative potential in TBI has not been reviewed yet. Therefore, in the present article, we present a comprehensive data on the important attributes of MSCs, such as neurotransdifferentiation, neuroprotection, axonal repair and plasticity, maintenance of blood-brain integrity, reduction of reactive oxygen species (ROS) and immunomodulation. We have reviewed in detail the crucial neurogenic capabilities of MSCs in vivo and provided consolidated knowledge regarding their cellular remodeling in TBI for future therapeutic implications.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
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*
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 Mesenchymal Stem Cell Expressing TRAIL as Targeted Therapy against Sensitised Tumour

Fakiruddin KS, Ghazalli N, Lim MN, Zakaria Z, Abdullah S

Int J Mol Sci, 2018 07 27;19(8).
PMID: 30060445 DOI: 10.3390/ijms19082188

Tapping into the ability of engineered mesenchymal stem cells (MSCs) to mobilise into the tumour has expanded the scope of cancer treatment. Engineered MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) could serve as a platform for an efficient and targeted form of therapy. However, the presence of cancer stem cells (CSCs) that are resistant to TRAIL and apoptosis may represent a challenge for effective treatment. Nonetheless, with the discovery of small molecular inhibitors that could target CSCs and tumour signalling pathways, a higher efficacy of MSC-TRAIL mediated tumour inhibition can be achieved. This might pave the way for a more effective form of combined therapy, which leads to a better treatment outcome. In this review, we first discuss the tumour-homing capacity of MSCs, its effect in tumour tropism, the different approach behind genetically-engineered MSCs, and the efficacy and safety of each agent delivered by these MSCs. Then, we focus on how sensitisation of CSCs and tumours using small molecular inhibitors can increase the effect of these cells to either TRAIL or MSC-TRAIL mediated inhibition. In the conclusion, we address a few questions and safety concerns regarding the utilization of engineered MSCs for future treatment in patients.

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*
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*

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