Etanercept-synthesizing adipose-derived stem cell secretome:A promising therapeutic option for inflammatory bowel disease

BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its pathogenesis.Etanercept,a decoy receptor for TNF,is used to treat inflammatory conditions.The secretome derived from adipose-derived stem cells(ASCs)has anti-inflammatory effects,making it a promising therapeutic option for IBD.AIM To investigate the anti-inflammatory effects of the secretome obtained from ASCs synthesizing etanercept on colon cells and in a dextran sulfate sodium(DSS)-induced IBD mouse model.METHODS ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing cells.The secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse model.RESULTS This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing ASCs[Etanercept-Secretome(Et-Sec)group]had significantly lower expression levels of inflammatory mediators,such as interleukin-6,Monocyte Chemoattractant Protein-1,and TNF-α,when compared to the control secretome(Ct-Sec).Moreover,the Et-Sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the Ct-Sec.CONCLUSION These results suggest that the secretome derived from ASCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD,potentially enhancing treatment efficacy by merging the anti-inflam-matory qualities of the ASC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.

Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model

BACKGROUND Globally,complete neurological recovery of spinal cord injury(SCI)is still less than 1%,and 90%experience permanent disability.The key issue is that a pharmacological neuroprotective-neuroregenerative agent and SCI regeneration mechanism have not been found.The secretomes of stem cell are an emerging neurotrophic agent,but the effect of human neural stem cells(HNSCs)secretome on SCI is still unclear.AIM To investigate the regeneration mechanism of SCI and neuroprotective-neuroregenerative effects of HNSCs-secretome on subacute SCI post-laminectomy in rats.METHODS An experimental study was conducted with 45 Rattus norvegicus,divided into 15 normal,15 control(10 mL physiologic saline),and 15 treatment(30μL HNSCssecretome,intrathecal T10,three days post-traumatic).Locomotor function was evaluated weekly by blinded evaluators.Fifty-six days post-injury,specimens were collected,and spinal cord lesion,free radical oxidative stress(F2-Isoprostanes),nuclear factor-kappa B(NF-κB),matrix metallopeptidase 9(MMP9),tumor necrosis factor-alpha(TNF-α),interleukin-10(IL-10),transforming growth factor-beta(TGF-β),vascular endothelial growth factor(VEGF),B cell lymphoma-2(Bcl-2),nestin,brain-derived neurotrophic factor(BDNF),glial cell line-derived neurotrophic factor(GDNF)were analyzed.The SCI regeneration mechanism was analyzed using partial least squares structural equation modeling(PLS SEM).RESULTS HNSCs-secretome significantly improved locomotor recovery according to Basso,Beattie,Bresnahan(BBB)scores and increased neurogenesis(nestin,BDNF,and GDNF),neuroangiogenesis(VEGF),anti-apoptotic(Bcl-2),anti-inflammatory(IL-10 and TGF-β),but decreased proinflammatory(NF-κB,MMP9,TNF-α),F2-Isoprostanes,and spinal cord lesion size.The SCI regeneration mechanism is valid by analyzed outer model,inner model,and hypothesis testing in PLS SEM,started with pro-inflammation followed by anti-inflammation,anti-apoptotic,neuroangiogenesis,neurogenesis,and locomotor function.CONCLUSION HNSCs-secretome as a potential neuroprotective-neuroregenerative agent for the treatment of SCI and uncover the SCI regeneration mechanism.

Human retinal secretome:A cross-link between mesenchymal and retinal cells

In recent years,mesenchymal stem cells(MSC)have been considered the most effective source for regenerative medicine,especially due to released soluble paracrine bioactive components and extracellular vesicles.These factors,collectively called the secretome,play crucial roles in immunomodulation and in improving survival and regeneration capabilities of injured tissue.Recently,there has been a growing interest in the secretome released by retinal cytotypes,especially retinal pigment epithelium and Müller glia cells.The latter trophic factors represent the key to preserving morphofunctional integrity of the retina,regulating biological pathways involved in survival,function and responding to injury.Furthermore,these factors can play a pivotal role in onset and progression of retinal diseases after damage of cell secretory function.In this review,we delineated the importance of cross-talk between MSCs and retinal cells,focusing on common/induced secreted factors,during experimental therapy for retinal diseases.The cross-link between the MSC and retinal cell secretomes suggests that the MSC secretome can modulate the retinal cell secretome and vice versa.For example,the MSC secretome can protect retinal cells from degeneration by reducing oxidative stress,autophagy and programmed cell death.Conversely,the retinal cell secretome can influence the MSC secretome by inducing changes in MSC gene expression and phenotype.

The secretome of endothelial progenitor cells: a potential therapeutic strategy for ischemic stroke

Ischemic stroke continues to be a leading cause of mortality and morbidity in the world. Despite recent advances in the field of stroke medicine, thrombolysis with recombinant tissue plasminogen activator remains as the only pharmacological therapy for stroke patients. However, due to short therapeutic window(4.5 hours of stroke onset) and increased risk of hemorrhage beyond this point, each year globally less than 1% of stroke patients receive this therapy which necessitate the discovery of safe and efficacious therapeutics that can be used beyond the acute phase of stroke. Accumulating evidence indicates that endothelial progenitor cells(EPCs), equipped with an inherent capacity to migrate, proliferate and differentiate, may be one such therapeutics. However, the limited availability of EPCs in peripheral blood and early senescence of few isolated cells in culture conditions adversely affect their application as effective therapeutics. Given that much of the EPC-mediated reparative effects on neurovasculature is realized by a wide range of biologically active substances released by these cells, it is possible that EPC-secretome may serve as an important therapeutic after an ischemic stroke. In light of this assumption, this review paper firstly discusses the main constituents of EPC-secretome that may exert the beneficial effects of EPCs on neurovasculature, and then reviews the currently scant literature that focuses on its therapeutic capacity.

Mesenchymal stem cells secretome:The cornerstone of cell-free regenerative medicine

Mesenchymal stem cells(MSCs)are the most frequently used stem cells in clinical trials due to their easy isolation from various adult tissues,their ability of homing to injury sites and their potential to differentiate into multiple cell types.However,the realization that the beneficial effect of MSCs relies mainly on their paracrine action,rather than on their engraftment in the recipient tissue and subsequent differentiation,has opened the way to cell-free therapeutic strategies in regenerative medicine.All the soluble factors and vesicles secreted by MSCs are commonly known as secretome.MSCs secretome has a key role in cell-to-cell communication and has been proven to be an active mediator of immunemodulation and regeneration both in vitro and in vivo.Moreover,the use of secretome has key advantages over cell-based therapies,such as a lower immunogenicity and easy production,handling and storage.Importantly,MSCs can be modulated to alter their secretome composition to better suit specific therapeutic goals,thus,opening a large number of possibilities.Altogether these advantages now place MSCs secretome at the center of an important number of investigations in different clinical contexts,enabling rapid scientific progress in this field.

Structural and functional aspects of the Helicobacter pylori secretome

Proteins secreted by Helicobacter pylori (H. pylori), an important human pathogen responsible for severe gastric diseases, are reviewed from the point of view of their biochemical characterization, both functional and structural. Despite the vast amount of experimental data available on the proteins secreted by this bacterium, the precise size of the secretome remains unknown. In this review, we consider as secreted both proteins that contain a secretion signal for the periplasm and proteins that have been detected in the external medium in in vitro experiments. In this way, H. pylori’s secretome appears to be composed of slightly more than 160 proteins, but this number must be considered very cautiously, not only because the definition of secretome itself is ambiguous but also because the included proteins were observed as secreted in in vitro experiments that were not representative of the environmental situation in vivo. The proteins that appear to be secreted can be grouped into different classes: enzymes (48 proteins), outer membrane proteins (43), components of flagella (11), members of the cytotoxic-associated genes pathogenicity island or other toxins (8 and 5, respectively), binding and transport proteins (9), and others (11). A final group, which includes 28 members, is represented by hypothetical uncharacterized proteins. Despite the large amount of data accumulated on the H. pylori secretome, a considerable amount of work remains to reach a full comprehension of the system at the molecular level.

Ameliorating liver fibrosis in an animal model using the secretome released from miR-122-transfected adipose-derived stem cells

BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,called secretome,rather than cells,has been evaluated for overcoming the limitations of cell-based therapy,while maintaining its advantages.However,the use of na?ve secretome may not fully satisfy the specificity of each disease.Therefore,it appears to be more advantageous to use the functionally reinforced secretome through a series of processes involving physico-chemical adjustments or genetic manipulation rather than to the use na?ve secretome.AIM To determine the therapeutic potential of the secretome released from miR-122-transfected adipose-derived stromal cells(ASCs).METHODS We collected secretory materials released from ASCs that had been transfected with antifibrotic miR-122(MCM)and compared their antifibrotic effects with those of the na?ve secretome(CM).MCM and CM were intravenously administered to the mouse model of thioacetamide-induced liver fibrosis,and their therapeutic potentials were compared.RESULTS MCM infusion provided higher therapeutic potential in terms of:(A)Reducing collagen content in the liver;(B)Inhibiting proinflammatory cytokines;and(C)Reducing abnormally elevated liver enzymes than the infusion of the na?ve secretome.The proteomic analysis of MCM also indicated that the contents of antifibrotic proteins were significantly elevated compared to those in the na?ve secretome.CONCLUSION We could,thus,conclude that the secretome released from miR-122-transfected ASCs has higher antifibrotic and anti-inflammatory properties than the na?ve secretome.Because miR-122 transfection into ASCs provides a specific way of potentiating the antifibrotic properties of ASC secretome,it could be considered as an enhanced method for reinforcing secretome effectiveness.

Generation of induced secretome from adipose-derived stem cells specialized for disease-specific treatment:An experimental mouse model

BACKGROUND Recently,the exclusive use of mesenchymal stem cell(MSC)-secreted molecules,named as the secretome,have been evaluated for overcoming the limitations of cell-based therapy while maintaining its advantages.AIM To improve cell-free therapy by adding disease-specificity through stimulation of MSCs using disease-causing materials.METHODS We collected the secretory materials(named as inducers)released from AML12 hepatocytes that had been pretreated with thioacetamide(TAA)and generated the TAA-induced secretome(TAA-isecretome)after stimulating adipose-derived stem cells with the inducers.The TAA-isecretome was intravenously administered to mice with TAA-induced hepatic failure and those with partial hepatectomy.RESULTS TAA-isecretome infusion showed higher therapeutic potential in terms of(1)restoring disorganized hepatic tissue to normal tissue;(2)inhibiting proinflammatory cytokines(interleukin-6 and tumor necrosis factor-α);and(3)reducing abnormally elevated liver enzymes(aspartate aminotransferase and alanine aminotransferase)compared to the naïve secretome infusion in mice with TAA-induced hepatic failure.However,the TAA-isecretome showed inferior therapeutic potential for restoring hepatic function in partially hepatectomized mice.Proteomic analysis of TAA-isecretome identified that antioxidant processes were the most predominant enriched biological networks of the proteins exclusively identified in the TAA-isecretome.In addition,peroxiredoxin-1,a potent antioxidant protein,was found to be one of representative components of TAA-isecretome and played a central role in the protection of TAA-induced hepatic injury.CONCLUSION Appropriate stimulation of adipose-derived stem cells with TAA led to the production of a secretome enriched with proteins,especially peroxiredoxin-1,with higher antioxidant activity.Our results suggest that appropriate stimulation of MSCs with pathogenic agents can lead to the production of a secretome specialized for protecting against the pathogen.This approach is expected to open a new way of developing various specific therapeutics based on the high plasticity and responsiveness of MSCs.

Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice

BACKGROUND Inflammatory bowel diseases(IBD)is related to uncontrolled immune response.Currently,there is no successful treatment for significant improvement in IBD.Stem cells display their therapeutic effects through their repopulating capacity or secreting factors.AIM To investigate the effects of conditioned mouse adipose-derived stem cells(mADSCs)secretome on colitis-induced mice.METHODS mADSCs were isolated from adipose tissue of C57BL/6 mice.Conditioned mADSCs secrectome was obtained by culturing of mADSCs with lipopolysaccharides(LPS,1μg/mL)for 24 h.Acute colitis was induced by 2%dextran sulfate sodium(DSS)drinking water for 7 d and then normal drinking water for 4 d.The mice were treated with normal culture medium(NM group),conditioned mADSCs secretome(CM group)or mADSCs(SC group).The length of colon and histopatholgy of colon tissues were evaluated.The mRNA expression levels of inflammatory cytokines in colon tissue and the serum interleukin(IL)-6 levels were determined.RESULTS The isolated mADSCs maintained the mADSCs specific gene expression profiles during experiment.The conditioned mADSCs secretome released by the treatment of mADSCs with LPS contained mainly inflammatory chemokines,colony-stimulating factors and inflammatory cytokines.The loss of body weight and reduction in colon length were ameliorated in the CM group.The conditioned mADSCs secretome reduced the histological score in colon tissue.The expression of IL-1b and IL-6 mRNAs in colon tissues significantly inhibited in the CM group compared to SC group and NM group,respectively.The elevation of serum IL-6 levels was also ameliorated in the CM group.These results indicate that the conditioned mADSCs secretome suppressed the synthesis of inflammatory cytokines in damaged colon tissue and the elevation of serum IL-6 concentration in DSS-induced mice CONCLUSION Conditioned mADSCs secretome might play regenerative roles by the suppression of IL-6 in serum and tissue during acute colitis,and may be more effective than stem cells themselves in the regeneration of colon tissue.

Mesenchymal stem cells,secretome and biomaterials in in-vivo animal models:Regenerative medicine application in cutaneous wound healing

The treatment of nonhealing and chronic cutaneous wounds still needs a clinical advancement to be effective.Both mesenchymal stem cells(MSCs),obtained from different sources,and their secretome derived thereof(especially exosomes)can activate signaling pathways related to promotion of cell migration,vascularization,collagen deposition,and inflammatory response demonstrating prohealing,angiogenetic and anti-scarring capacities.On the other hand,biodegradable biomimetic scaffolds can facilitate endogenous cell attachment and proliferation as well as extracellular matrix production.In this Review,we revise the complex composites made by biomimetic scaffolds,mainly hydrogels,and MSC-derived exosomes constructed for cutaneous wound healing.Studies demonstrate that there exists a synergistic action of scaffolds with encapsulated exosomes,displaying a sustained release profiles to facilitate longlasting healing effects.It can be envisioned that dressings made by biomimetic hydrogels and MSC-derived exosomes will be clinically applied in the near future for the effective treatment of nonhealing and chronic wounds.

Disagreements in the therapeutic use of mesenchymal stem cellderived secretome

In a recent article,the authors provide a detailed summary of the characteristics and biological functions of mesenchymal stem cells(MSCs),as well as a discussion on the potential mechanisms of action of MSC-based therapies.They describe the morphology,biogenesis,and current isolation techniques of exosomes,one of the most important fractions of the MSC-derived secretome.They also summarize the characteristics of MSC-derived exosomes and highlight their functions and therapeutic potential for tissue/organ regeneration and for kidney,liver,cardiovascular,neurological,and musculoskeletal diseases,as well as cutaneous wound healing.Despite the fact that MSCs are regarded as an important pillar of regenerative medicine,their regenerative potential has been demonstrated to be limited in a number of pathological conditions.The negative effects of MSC-based cell therapy have heightened interest in the therapeutic use of MSC-derived secretome.On the other hand,MSC-derived exosomes and microvesicles possess the potential to have a significant impact on disease development,including cancer.MSCs can interact with tumor cells and promote mutual exchange and induction of cellular markers by exchanging secretome.Furthermore,enzymes secreted into and activated within exosomes can result in tumor cells acquiring new properties.As a result,therapeutic applications of MSC-derived secretomes must be approached with extreme caution.

Controversies in therapeutic application of mesenchymal stem cell-derived secretome

Though mesenchymal stem cells(MSCs)are considered as an important pillar of regenerative medicine,their regenerative potential has been shown to be limited in several pathological conditions.The adverse properties of MSCbased cell therapy have drawn attention to the therapeutic use of MSC-derived secretome.However,MSC-originated exosomes and microvesicles can also possess a significant impact on disease development,including cancer.By interchanging secretome,MSCs can interact with tumor cells and promote mutual exchange/induction of cellular markers.In addition,enzymes secreted into and activated within exosomes can result in the acquisition of new tumor cell properties.Therefore,therapeutic applications of MSC-derived secretome require much caution.

Inhibition mechanisms of secretome proteins from Paenibacillus polymyxa Kp10 and Lactococcus lactis Gh1 against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus

Objective:To determine the inhibition mechanisms of secretome protein extracted from Paenibacillus polymyxa Kp10(Kp10)and Lactococcus lactis Gh1(Gh1)against methicillin-resistant Staphylococcus aureus(MRSA)and vancomycin-resistant Enterococcus(VRE).Methods:The sensitivity and viability of MRSA and VRE treated with secretome proteins of Kp10 and Gh1 were determined using minimal inhibitory concentration,minimum bactericidal concentration,and time-to-kill assays.The morphological changes were observed using scanning electron microscopy and transmission electron microscopy.To elucidate the antimicrobial mechanism of secretome protein of Kp10 and Gh1 against MRSA and VRE,2D gel proteomic analysis using liquid chromatography-mass spectrometry was run by comparing upregulated and downregulated proteins,and the proton motive force study including the efflux of ATP,pH gradient,and the membrane potential study were conducted.Results:MRSA and VRE were sensitive to Kp10 and Gh1 secretome protein extracts and displayed apparent morphological and internal composition changes.Several proteins associated with cellular component functions were either downregulated or upregulated in treated MRSA and VRE by changing the membrane potential gradient.Conclusions:Kp10 and Gh1 secretome proteins reduce the growth of VRE and MRSA by damaging the cell membrane.Cell division,cell wall biosynthesis,and protein synthesis are involved in the inhibition mechanism.

Secretome-microRNA and anti-proliferative APRO family proteins as cancer prevention and stem cell research strategies

Stemness of cancer cells contains limitless self-renewal proliferation.For the purpose of proliferation,secretome might exert its effects via the paracrine signaling.Specific microRNAs enclosed in the secretome of cancer stem cells could regulate the expression of anti-proliferative APRO family proteins.The biological functions of APRO family proteins seems to be quite intricate,however,which might be a key modulator of microRNAs,then could regulate the proliferation of cancer cells.In addition to affecting proliferation/differentiation during cellular development,APRO family proteins might also play an imperious role on keeping homeostasis in healthy stem cells under a physiological condition.Therefore,relationship between the microRNAs and the APRO family proteins has attracted much attention in the field of cancer research and regenerative medicine.Here,we have described the molecular mechanism behind this interplay that have a potential role in the future promising tools with targeting APRO family proteins for the medical applications.

Mesenchymal stem cell secretome and nanotechnology:Combining therapeutic strategies

Mesenchymal stem cells(MSC)have pushed the field of stem cell-based therapies by inducing tissue regeneration,immunosuppression,and angiogenesis mainly through vesicles and soluble factors release(paracrine signaling).MSC-extracellular vesicles(MSC-EV)adaptable secretome and homing to injured sites allowed researchers to unlock a new era of cell-free based therapy.In parallel,nanoparticles(NP)have been explored in contributing to transport and drug delivery systems,giving drugs desired physical-chemical properties to exploit cell behavior.However,NPs can be quickly recognized by immune cells and cleared from circulation.In this viewpoint,we explore how combining both therapeutic strategies can improve efficacy and circumvent limitations of both therapies.MSCEV benefit from the potent MSC membrane composition,guiding chemotaxis to tumor sites,a very restricted microenvironment.MSC-EV has low immunogenicity,high stability,long half-life and can explore tissue targeting ligands as a precise drug carry,even across biological barriers.Those properties promote enhanced targeted drug delivery that can be combined with NP,exploring biological membrane production through:1.direct cell therapy with NP-infused MSC;2.NP-containing MSC-EV generated by NP-infused MSC;3.by coating NP in MSC membrane(“MSC NanoGhosts”),allowing precise cargo definition without losing targeting.Therefore,nanotechnology combined with cell-based therapeutic resources can greatly improve targeted drug delivery,improving efficacy and opening a new venue of therapeutic possibilities.

Tuning mesenchymal stem cell secretome therapeutic potential through mechanotransduction

Mesenchymal stem cells(MSCs)and their byproducts have been widely validated as potential therapeutic products for regenerative medicine.The therapeutic effects result mainly from the paracrine activity of MSCs,which consists of the secretion of bioactive molecules,whether dispersed in medium conditioned by cell culture or encapsulated in extracellular vesicles.The composition of the MSC secretome,which represents the set of these secreted cellular products,is crucial for the performance of the desired therapeutic functions.Different cell culture strategies have been employed to adjust the secretome composition of MSCs to obtain the best therapeutic responses for different clinical contexts.However,the manipulation of culture conditions has focused mainly on the use of different biochemical elements for the preconditioning of MSCs and less on the physical conditions of the cell culture environment.Herein,we offer our point of view regarding the importance of the physical properties of cell culture substrates and their mechanotransduction responses in preconditioning the MSCs secretome.We highlight the relevance of studying mechanotransduction events associating cell morphology and the modulation of gene expression to customize and expand the use of MSCs secretomes.

Mesenchymal stem cells derived secretome as an innovative cell-free therapeutic approach

The paracrine and immunomodulatory cytokines secreted by mesenchymal stem cells(MSCs),generally referred to as the MSCs derived secretome,has substantial potential for the treatment of many chronic and degenerative diseases.MSCs secretome contains both common and disease specific cytokines and modulators that can be beneficial against a wide range of chronic diseases.Herein,we discuss the MSCs secretome composition profile and its translational applicability and the challenges surrounding its use in clinical settings.

Mesenchymal stem cells,the secretome and biomaterials:Regenerative medicine application

Mesenchymal stem cells(MSCs)are multipotent cells usually isolated from bone marrow,endometrium,adipose tissues,skin,and dental pulp.MSCs played a crucial role in regenerative therapy and have been introduced as an interdisciplinary field between cell biology and material science.Recently,MSCs have been widely explored for their application in regenerative medicine and COVID-19 treatment.Different approaches to evaluate the future of biomaterials and stem cell properties have been developed.However,misconceptions and ethical issues still exist,such as MSCs being non-angiogenic,anti-apoptotic,and immunoregulatory competencies.Embryonic stem cells isolation primarily requires the consent of donors and can include the killing of fertilized eggs.These issues generate questions related to ethical and moral issues.However,MSCs have gained considerable attention for tissue regeneration owing to their differentiation ability with immunomodulatory effects.They are capable of secreting a broad range of biomolecules such as proteins,nucleic acids,exosomes,microRNAs,and membrane vesicles,collectively known as secretomes.Secretomes are released in response to the surrounding microenvironment.In this article,we briefly address topics related to the therapeutic potential of MSCs as an advanced approach in the field of regenerative medicine and various perspectives.

Production of mesenchymal stem cell derived-secretome as cell-free regenerative therapy and immunomodulation:A biomanufacturing perspective

The potential of mesenchymal stem cells(MSCs)in regenerative medicine has been largely known due to their capability to induce tissue regeneration in vivo with minimum inflammation during implantation.This adult stem cell type exhibit unique features of tissue repair mechanism and immune modulation mediated by their secreted factors,called secretome.Recently,the utilization of secretome as a therapeutic agent provided new insight into cell-free therapy.Nevertheless,a sufficient amount of secretome is necessary to realize their applications for translational medicine which required a proper biomanufacturing process.Several factors related to their production need to be considered to produce a clinical-grade secretome as a biological therapeutic agent.This viewpoint highlights the current challenges and considerations during the biomanufacturing process of MSCs secretome.

Evaluation of the Secretome Profile and Functional Characteristics of Human Bone Marrow Mesenchymal Stromal Cells-Derived Conditioned Medium Suggest Potential for Skin Rejuvenation

Background/Purpose: Multipotent bone marrow-derived mesenchymal stromal cells (BMMSC) have been shown to possess the potential for tissue regeneration. The application of mesenchymal stromal cells (MSC)-derived growth factors and cytokines (GF/CKs) has been implicated for the repair and regeneration of the damaged skin that occurs due to aging and exposure to environmental stress factors. Methods: We have used both qualitative and quantitative measurements of the GF/CKs from the conditioned medium (CM) of a pooled population of BMMSC by antibody array analysis as well as by enzyme-linked immunosorbent assay (ELISA). Furthermore, the CM was also used in a variety of in vitro biological assays to measure its protective properties in human skin fibroblasts. Results: We have characterized the secretome of BMMSC by analyzing the composition of the CM using a forty-one growth factor array system. Thirteen of these GF/CK/extra cellular matrix (ECM)/ matrix metalloproteinases (MMP)-inhibitors in the CM were quantified owing to their involvement in skin repair cascade. In addition, we report that the BMMSC-CM was also able to protect dermal fibroblasts against tert-Butyl hydro peroxide (tbOH) induced oxidative stress and ultra violet B (UV-B) radiation induced cell damage. Conclusion: Based on the data presented here, we propose that BMMSC-derived CM may have the potential to promote health and rejuvenation of the aging skin.