Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine

Gunawardena, Tarini; Rahman, Mohammad Tariqur; Abdullah, Basri Johan Jeet; Kasim, Noor Hayaty Abu

doi:10.1002/term.2806

Cited by 102 publications

(85 citation statements)

References 129 publications

(150 reference statements)

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“…Color images are available online. therapies, 24 and our results show that secreted factors from MSTCs may be able to serve a similar function. In addition, MSTCs may serve both as source and the recipient of MSTC-derived paracrine signaling.…”

Section: Discussionsupporting

confidence: 63%

Skin Microcolumns as a Source of Paracrine Signaling Factors

Tam

Purschke

Fuchs

et al. 2020

Advances in Wound Care

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We recently developed the approach of using ''microcolumns'' of autologous full-thickness skin tissue for wound repair. The small size of these micro skin tissue columns (MSTCs, *0.5 mm in diameter) allows donor sites to heal quickly without scarring. Treatment with MSTCs significantly accelerate wound healing, and suppled various skin cell types and skin structures to replenish the wound volume. This technology is now starting clinical use. In this study, we investigate whether MSTCs may also influence wound healing by releasing soluble signaling factors. Approach: Freshly harvested MSTCs were incubated in culture medium for 24 h. The conditioned medium was collected and tested for its effects on migration and proliferation of human dermal fibroblasts, and its ability to induce tube formation by human umbilical vein endothelial cells (HUVECs). Proteins released into the conditioned medium were characterized by multiplex enzymelinked immunosorbent assay (ELISA), and compared with medium conditioned by an equivalent mass of intact full-thickness skin. Results: MSTC-conditioned medium increased fibroblast migration and proliferation, as well as HUVEC tube formation. MSTCs released many soluble factors known to play prominent roles in wound healing. A subset of proteins showed significantly different release profiles compared with intact full-thickness skin. Innovation: The technology for harvesting and using MSTCs to augment wound healing was recently developed as an alternative to conventional autologous skin grafting. This study shows that MSTCs could also function as ''cytokine factories.'' Conclusion: In addition to supplying autologous cells to repopulate the wound volume, MSTCs can also function as a source of growth factors and cytokines to further enhance wound healing.

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Section: Discussionsupporting

confidence: 63%

Skin Microcolumns as a Source of Paracrine Signaling Factors

Tam

Purschke

Fuchs

et al. 2020

Advances in Wound Care

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“…Other research approaches have highlighted the role of the SMAD pathway and mitogen-activated protein kinase (via Runx2 transcription activation) in the differentiation and mineralization of bone marrow MSCs in vitro . It has been shown that paracrine factors are maintained at a high level by conditioned media derived from MSC cultures; this might help to speed recovery and the bone healing process in general (Gunawardena, Rahman, Abdullah, & Abu Kasim, 2019).…”

Section: Targetsmentioning

confidence: 99%

The Masquelet technique: Current concepts, animal models, and perspectives

Klein

Monet

Barbier

et al. 2020

J Tissue Eng Regen Med

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Bone reconstruction within a critical‐sized defect remains a real challenge in orthopedic surgery. The Masquelet technique is an innovative, two‐step therapeutic approach for bone reconstruction in which the placement of a poly (methylmethacrylate) spacer into the bone defect induces the neo‐formation of a tissue called “induced membrane.” This surgical technique has many advantages and is often preferred to a vascularized bone flap or Ilizarov's technique. Although the Masquelet technique has achieved high clinical success rates since its development by Alain‐Charles Masquelet in the early 2000s, very little is known about how the process works, and few animal models of membrane induction have been developed. Our successful use of this technique in the clinic and our interest in the mechanisms of tissue regeneration (notably bone regeneration) prompted us to develop a surgical model of the Masquelet technique in rats. Here, we provide a comprehensive review of the literature on animal models of membrane induction, encompassing the defect site, the surgical procedure, and the histologic and osteogenic properties of the induced membrane. We also discuss the advantages and disadvantages of those models to facilitate efforts in characterizing the complex biological mechanisms that underlie membrane induction.

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“…Therefore, the pre-conditioning with preservation solution has been demonstrated to be a promising method to protect donor hearts against I/R injuryinduced graft dysfunction via the inhibition of in ammation and apoptosis. Recently, an increasing number of studies have demonstrated that BMSCs can secrete a vast array of paracrine factors, including cytokines, microRNA, growth factors, antioxidants, proteasomes, and exosomes (32), which are thought to be responsible for the observed cardioprotective effects for I/R injury-induced infarcted hearts in myocardial infarction (13,33), brain-dead(23) and older(15) donor hearts in a rat heart transplantation model. In the present study, our antibodybased protein array analyses showed that the normoxic CM-BMSCs isolated by our group contained various kinds of cytokines, including Monocyte Chemoattractant Protein-1 (MCP-1), Tissue Inhibitor of Metalloproteinase (TIMP)-1, Interleukin-10 (IL-10), Decorin, Activin A, Galectin-1, HGF, Interleukin-6 (IL-6), VEGF, which may be involved in cardiac protection and functional improvement observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Donor Heart Preservation with Hypoxic Conditioned Medium Derived from Bone Marrow Mesenchymal Stem cell improves Cardiac Function in a Heart Transplantation Model

Zhou

Liu

et al. 2020

Preprint

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Background: In heart transplantation, donor hearts inevitably suffer from ischemia/reperfusion (I/R) injury, which leads to primary graft dysfunction and affects patients’ survival rate. Bone marrow mesenchymal stem cells (BMSCs) have been reported to attenuate myocardial I/R injury via their paracrine effects, which can be enhanced by hypoxic preconditioning. We hypothesized that the donor heart preservation with hypoxic conditioned medium derived from BMSCs (CM-BMSCs) would improve post-transplant graft function. Methods: Normoxic CM and hypoxic CM were isolated from rat BMSCs cultured under normoxic (20% O2) or hypoxic (1% O2) condition. Donor hearts were explanted, stored in cardioplegic solution supplemented with either a medium (Vehicle), normoxic CM (N-CM), or hypoxic CM (H-CM), and then heterotopically transplanted. Antibody arrays were performed to compare the differences between hypoxic CM and normoxic CM.Results: After heart transplantation, the donor heart preservation with normoxic CM was associated with shorter re-beating time, histopathological scores, and left ventricular systolic diameter, higher ejection fraction, and fractional shortening of transplanted hearts. These protective effects may be associated with the inhibition of apoptosis and inflammation, as reflected by less TUNEL-positive cells and lower levels of serum proinflammatory cytokines (Interleukin-1β, Interleukin-6, tumor necrosis factor-α) and cardiac troponin I in the N-CM group compared with the vehicle group. These therapeutic effects can be further enhanced by hypoxic preconditioning. Antibody arrays revealed that nine proteins were significantly increased in hypoxic CM compared with normoxic CM. Furthermore, compared with vehicle and N-CM groups, the protein levels of PI3K and p‐Akt/Akt ratio in the transplanted hearts significantly increased in the H-CM group. Conclusions: Our results indicate that cardioplegic solution-enriched with hypoxic CM-BMSCs can be a novel and promising preservation solution for donor hearts.

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Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine

Cited by 102 publications

References 129 publications

Skin Microcolumns as a Source of Paracrine Signaling Factors

Skin Microcolumns as a Source of Paracrine Signaling Factors

The Masquelet technique: Current concepts, animal models, and perspectives

Donor Heart Preservation with Hypoxic Conditioned Medium Derived from Bone Marrow Mesenchymal Stem cell improves Cardiac Function in a Heart Transplantation Model

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