MyMedR

Strategy for generating tissue-engineered human bone construct

Tan KK, Aminuddin BS, Tan GH, Sabarul Afian M, Ng MH, Fauziah O, et al.

Med J Malaysia, 2004 May;59 Suppl B:43-4.

The strategy used to generate tissue-engineered bone construct, in view of future clinical application is presented here. Osteoprogenitor cells from periosteum of consenting scoliosis patients were isolated. Growth factors viz TGF-B2, bFGF and IGF-1 were used in concert to increase cell proliferation during in vitro cell expansion. Porous tricalcium phosphate (TCP)-hydroxyapatite (HA) scaffold was used as the scaffold to form 3D bone construct. We found that the addition of growth factors, greatly increased cell growth by 2 to 7 fold. TCP/HA proved to be the ideal scaffold for cell attachment and proliferation. Hence, this model will be further carried out on animal trial.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*

The use of bone marrow stem cells for bone tissue engineering

Ng MH, Aminuddin BS, Tan KK, Tan GH, Sabarul Afian M, Ruszymah BH

Med J Malaysia, 2004 May;59 Suppl B:41-2.

PMID: 15468809

Bone marrow stem cells (BMSC), known for its multipotency to differentiate into various mesenchymal cells such as chodrocyte, osteoblasts, adipocytes, etc, have been actively applied in tissue engineering. BMSC have been successfully isolated from bone marrow aspirate and bone marrow scraping from patients of various ages (13-56 years) with as little as 2ml to 5ml aspirate. BMSC isolated from our laboratory showed the presence of a heterogenous population that showed varying prevalence of surface antigens and the presence of telomerase activity albeit weak. Upon osteogenic induction, alkaline phosphatase activity and mineralization activity were observed.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*

Scaffolds in bone tissue engineering

Nather A

Med J Malaysia, 2004 May;59 Suppl B:37-8.

PMID: 15468807

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*

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-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*

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*

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*

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*

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 Stem Cell Transplantation*

Adult stem cells: a clinical update

Totey S, Totey S, Pal R, Pal R

J Stem Cells, 2009;4(2):105-21.

PMID: 20232596

There has been unprecedented interest in stem cell research mainly because of their true potential and hope that they offer to the patients as a cell therapy with the prospect to treat hitherto incurable diseases. Despite the worldwide interest and efforts that have been put in this research, major fundamental issues are still unresolved. Adult stem cells such as hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) are already under clinical applications and there are several examples of plasticity and self-renewal where adult stem cells or their precursor cells can be re-programmed by extra cellular cues or internal cues to alter their character in a way that could have important application for cell therapy and regenerative medicine. From a clinical perspective, no other area of stem cell biology has been applied as successfully as has transplantation of bone marrow stem cells and cord blood stem cells for the treatment of hematological diseases. In the last few years, research in stem cell biology has expanded staggeringly, engendering new perspectives concerning the identity, origin, and full therapeutic potential of tissue-specific stem cells. This review will focus on the use of adult stem cells, its biology in the context of cell plasticity and their therapeutic potential for repair of different tissues and organs.

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*

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*

Intramyocardial and intracoronary autologous bone marrow-derived mesenchymal stromal cell treatment in chronic severe dilated cardiomyopathy

Chin SP, Poey AC, Wong CY, Chang SK, Tan CS, Ng MT, et al.

Cytotherapy, 2011 Aug;13(7):814-21.

PMID: 21526902 DOI: 10.3109/14653249.2011.574118

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) may improve cardiac function following myocardial infarction. MSC can differentiate into cardiomyocytes and endothelial cells while exerting additional paracrine effects. There is limited information regarding the efficacy of route for MSC treatment of severe dilated cardiomyopathy (DCM). The aim of this study was to demonstrate the clinical safety, feasibility and efficacy of direct intramyocardial and intracoronary administration of autologous bone marrow-derived MSC treatment for no-option patients with chronic severe refractory DCM.

METHODS: Ten symptomatic patients with DCM and refractory cardiac function, despite maximum medical therapy, were selected. Five had ischemic DCM deemed unlikely to benefit from revascularization alone and underwent bypass operations with concurrent intramyocardial MSC injection (group A). Two patients had previous revascularization and three had non-ischemic DCM and received intracoronary MSC injection (group B).

RESULTS: Group A and B patients received 0.5-1.0 × 10(6) and 2.0-3.0 × 10(6) MSC/kg body weight, respectively. All patients remained alive at 1 year. There were significant improvements from baseline to 6 and 12 months in left ventricular ejection fraction and other left ventricular parameters. Scar reduction was noted in six patients by 12 months.

CONCLUSIONS: Autologous bone marrow MSC treatment is safe and feasible for treating chronic severe refractory DCM effectively, via intracoronary or direct intramyocardial administration at prescribed doses.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*

Fulltext A preliminary study comparing the use of allogenic chondrogenic pre-differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits

Dashtdar H, Rothan HA, Tay T, Ahmad RE, Ali R, Tay LX, et al.

J Orthop Res, 2011 Sep;29(9):1336-42.

PMID: 21445989 DOI: 10.1002/jor.21413

Chondrogenic differentiated mesenchymal stem cells (CMSCs) have been shown to produce superior chondrogenic expression markers in vitro. However, the use of these cells in vivo has not been fully explored. In this study, in vivo assessment of cartilage repair potential between allogenic-derived chondrogenic pre-differentiated mesenchymal stem cells and undifferentiated MSCs (MSCs) were compared. Bilateral full thickness cartilage defects were created on the medial femoral condyles of 12 rabbits (n = 12). Rabbits were divided into two groups. In one group, the defects in the right knees were repaired using alginate encapsulated MSCs while in the second group, CMSCs were used. The animals were sacrificed and the repaired and control knees were assessed at 3 and 6 months after implantation. Quantitative analysis was performed by measuring the Glycosaminoglycans (GAGs)/total protein content. The mean Brittberg score was higher in the transplanted knees as compared to the untreated knee at 6 months (p 0.05). This study demonstrates that the use of either MSC or CMSC produced superior healing when compared to cartilage defects that were untreated. However, both cells produced comparable treatment outcomes.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*

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*

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*

Fulltext The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model

Al Faqeh H, Nor Hamdan BM, Chen HC, Aminuddin BS, Ruszymah BH

Exp Gerontol, 2012 Jun;47(6):458-64.

PMID: 22759409 DOI: 10.1016/j.exger.2012.03.018

In recent years, the use of bone marrow mesenchymal stem cell (BMSC) implantation has provided an alternative treatment for osteoarthritis. The objective of this study is to determine whether or not an intra-articular injection of a single dose of autologous chondrogenic induced BMSC could retard the progressive destruction of cartilage in a surgically induced osteoarthritis in sheep. Sheep BMSCs were isolated and divided into two groups. One group was cultured in chondrogenic media containing (Ham's F12:DMEM, 1:1) FD+1% FBS+5 ng/ml TGFβ3+50 ng/ml IGF-1 (CM), and the other group was cultured in the basal media, FD+10% FBS (BM). The procedure for surgically induced osteoarthritis was performed on the donor sheep 6 weeks prior to intra-articular injection into the knee joint of a single dose of BMSC from either group, suspended in 5 ml FD at density of 2 million cells/ml. The control groups were injected with basal media, without cells. Six weeks after injection, gross evidence of retardation of cartilage destruction was seen in the osteoarthritic knee joints treated with CM as well as BM. No significant ICRS (International Cartilage Repair Society) scoring was detected between the two groups with cells. However macroscopically, meniscus repair was observed in the knee joint treated with CM. Severe osteoarthritis and meniscal injury was observed in the control group. Interestingly, histologically the CM group demonstrated good cartilage histoarchitecture, thickness and quality, comparable to normal knee joint cartilage. As a conclusion, intra-articular injection of a single dose of BMSC either chondrogenically induced or not, could retard the progression of osteoarthritis (OA) in a sheep model, but the induced cells indicated better results especially in meniscus regeneration.
Study site: Universiti Kebangsaan Malaysia, Kuala Lumpur

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*

Hyaluronic acid with or without bone marrow derived-mesenchymal stem cells improves osteoarthritic knee changes in rat model: a preliminary report

Suhaeb AM, Naveen S, Mansor A, Kamarul T

Indian J Exp Biol, 2012 Jun;50(6):383-90.

PMID: 22734248

Despite being a complex degenerative joint disease, studies on osteoarthritis (OA) suggest that its progression can be reduced by the use of hyaluronic acid (HA) or mesenchymal stem cells (MSC). The present study thus aims to examine the effects of MSC, HA and the combination of HA-MSC in treating OA in rat model. The histological observations using O'Driscoll score indicate that it is the use of HA and MSC independently and not their combination that delays the progression of OA. In conclusion, the preliminary study suggest that the use of either HA or MSCs effectively reduces OA progression better than their combined use.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*

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