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MSC in Tendon and Joint Disease: The Context-Sensitive Link Between Targets and Therapeutic MechanismsRoth, Susanne Pauline, Burk, Janina, Brehm, Walter, Troillet, Antonia 08 June 2023 (has links)
Mesenchymal stromal cells (MSC) represent a promising treatment option for tendon
disorders and joint diseases, primarily osteoarthritis. Since MSC are highly context-sensitive to their microenvironment, their therapeutic efficacy is influenced by their
tissue-specific pathologically altered targets. These include not only cellular
components, such as resident cells and invading immunocompetent cells, but also
components of the tissue-characteristic extracellular matrix. Although numerous in vitro
models have already shown potential MSC-related mechanisms of action in tendon and
joint diseases, only a limited number reflect the disease-specific microenvironment and
allow conclusions about well-directed MSC-based therapies for injured tendon and joint-associated tissues. In both injured tissue types, inflammatory processes play a pivotal
pathophysiological role. In this context, MSC-mediated macrophage modulation seems to
be an important mode of action across these tissues. Additional target cells of MSC
applied in tendon and joint disorders include tenocytes, synoviocytes as well as other
invading and resident immune cells. It remains of critical importance whether the context-sensitive interplay between MSC and tissue- and disease-specific targets results in an
overall promotion or inhibition of the desired therapeutic effects. This review presents the
authors’ viewpoint on disease-related targets of MSC therapeutically applied in tendon and
joint diseases, focusing on the equine patient as valid animal model.
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Functional properties of equine adipose-derived mesenchymal stromal cells cultured with equine platelet lysateHagen, Alina, Niebert, Sabine, Brandt, Vivian-Pascal, Holland, Heidrun, Melzer, Michaela, Wehrend, Axel, Burk, Janina 02 November 2023 (has links)
Successful translation of multipotent mesenchymal stromal cell (MSC)-based therapies into clinical reality relies on adequate cell production procedures. These should be available not only for human MSC, but also for MSC from animal species relevant to preclinical research and veterinary medicine. The cell culture medium supplementation is one of the critical aspects in MSC production. Therefore, we previously established a scalable protocol for the production of buffy-coat based equine platelet lysate (ePL). This ePL proved to be a suitable alternative to fetal bovine serum (FBS) for equine adipose-derived (AD-) MSC culture so far, as it supported AD-MSC proliferation and basic characteristics. The aim of the current study was to further analyze the functional properties of equine AD-MSC cultured with the same ePL, focusing on cell fitness, genetic stability and pro-angiogenic potency. All experiments were performed with AD-MSC from n = 5 horses, which were cultured either in medium supplemented with 10% FBS, 10% ePL or 2.5% ePL. AD-MSC cultured with 2.5% ePL, which previously showed decreased proliferation potential, displayed higher apoptosis but lower senescence levels as compared to 10% ePL medium (p < 0.05). Non-clonal chromosomal aberrations occurred in 8% of equine AD-MSC cultivated with FBS and only in 4.8% of equine AD-MSC cultivated with 10% ePL. Clonal aberrations in the AD-MSC were neither observed in FBS nor in 10% ePL medium. Analysis of AD-MSC and endothelial cells in an indirect co-culture revealed that the ePL supported the pro-angiogenic effects of AD-MSC. In the 10% ePL group, more vascular endothelial growth factor (VEGF-A) was released and highest VEGF-A concentrations were reached in the presence of ePL and co-cultured cells (p < 0.05). Correspondingly, AD-MSC expressed the VEGF receptor-2 at higher levels in the presence of ePL (p < 0.05). Finally, AD-MSC and 10% ePL together promoted the growth of endothelial cells and induced the formation of vessel-like structures in two of the samples. These data further substantiate that buffy-coat-based ePL is a valuable supplement for equine AD-MSC culture media. The ePL does not only support stable equine AD-MSC characteristics as demonstrated before, but it also enhances their functional properties.
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Platelet Lysate for Mesenchymal Stromal Cell Culture in the Canine and Equine Species: Analogous but Not the SameHagen, Alina, Holland, Heidrun, Brandt, Vivian-Pascal, Doll, Carla U., Häußler, Thomas C., Melzer, Michaela, Moellerberndt, Julia, Lehmann, Hendrik, Burk, Janina 02 June 2023 (has links)
Simple Summary
Regenerative medicine using platelet-based blood products or adult stem cells offers the prospect of better clinical outcomes with many diseases. In veterinary medicine, most progress has been made with the development and therapeutic use of these regenerative therapeutics in horses, but the clinical need is given in dogs as well. Our aim was to transfer previous advances in the development of horse regenerative therapeutics, specifically the use of platelet lysate for feeding stem cell cultures, to the dog. Here, we describe the scalable production of canine platelet lysate, which could be used in regenerative biological therapies. We also evaluated the canine platelet lysate for its suitability in feeding canine stem cell cultures in comparison to equine platelet lysate used for equine stem cell cultures. Platelet lysate production from canine blood was successful, but the platelet lysate did not support stem cell culture in dogs in the same beneficial way observed with the equine platelet lysate and stem cells. In conclusion, canine platelet lysate can be produced in large scales as described here, but further research is needed to improve the cultivation of canine stem cells.
Abstract
Platelet lysate (PL) is an attractive platelet-based therapeutic tool and has shown promise as xeno-free replacement for fetal bovine serum (FBS) in human and equine mesenchymal stromal cell (MSC) culture. Here, we established a scalable buffy-coat-based protocol for canine PL (cPL) production (n = 12). The cPL was tested in canine adipose MSC (n = 5) culture compared to FBS. For further comparison, equine adipose MSC (n = 5) were cultured with analogous equine PL (ePL) or FBS. During canine blood processing, platelet and transforming growth factor-β1 concentrations increased (p < 0.05 and p < 0.001), while white blood cell concentrations decreased (p < 0.05). However, while equine MSC showed good results when cultured with 10% ePL, canine MSC cultured with 2.5% or 10% cPL changed their morphology and showed decreased metabolic activity (p < 0.05). Apoptosis and necrosis in canine MSC were increased with 2.5% cPL (p < 0.05). Surprisingly, passage 5 canine MSC showed less genetic aberrations after culture with 10% cPL than with FBS. Our data reveal that using analogous canine and equine biologicals does not entail the same results. The buffy-coat-based cPL was not adequate for canine MSC culture, but may still be useful for therapeutic applications.
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An investigation into the potential of mesenchymal stromal cells to attenuate graft-versus-host diseaseMelinda Elise Christensen Unknown Date (has links)
Survival of patients with poor prognosis or relapsed haematopoietic malignancies can be markedly improved by allogeneic haematopoietic stem cell transplantation (HSCT). HSCT reconstitutes the immune and haematopoietic systems after myeloablative conditioning and inhibits the recurrence of the malignancy by a graft-versus-leukaemia (GVL) response mediated by donor T cells. However, significant post-transplant complications such as graft-versus-host disease (GVHD) continue to plague the event-free survival of this curative procedure. GVHD is facilitated by donor T cells that recognise histocompatibility antigens on host antigen presenting cells (APC), such as dendritic cells (DC). Current treatment options for GVHD are focused on these T cells. However, these treatments result in an increased incidence of infection, graft rejection and relapse. A novel means of immunosuppression in GVHD is the use of multi-potent, mesenchymal stromal cells (MSC). MSC are non-immunogenic cells that actively suppress T cell function in vitro, and can resolve steroid-refractory GVHD in the clinic. Despite their use in the clinic, there is a paucity of pre-clinical data. Our aim was to investigate the in vivo efficacy of MSC to control GVHD while maintaining the beneficial GVL effect, and to begin to understand the mechanism by which MSC exert their immunosuppressive effects. We isolated and characterised MSC from murine bone/bone marrow and demonstrated that they suppressed T cell proliferation in vitro, even at low ratios of 1 MSC per 100 T cells. This was true of both donor-derived MSC, and MSC derived from unrelated donors (third party). Importantly, we observed that MSC significantly reduced T cell production of the pro-inflammatory cytokines TNFα and IFNγ in culture supernatants and that IFNγ plays a key role in the ability of MSC to suppress T cell proliferation. In vivo, we examined the effects of donor-derived MSC on GVHD severity and onset in two myeloablative murine models of HSCT. A major histocompatibility complex (MHC)-mismatched donor-recipient pair combination was used as a proof–of-principle model [UBI-GFP/BL6 (H-2b)àBALB/c (H-2d)], and an MHC-matched, minor histocompatibility antigen (miHA) mismatched donor-recipient pair combination was used to mimic MHC-matched sibling transplantation [UBI-GFP/BL6 (H-2b)àBALB.B (H-2b)]. We examined a number of variables related to MSC infusion including timing, dose and route of injection. We found that early post transplant infusion of MSC by the intraperitoneal injection was most effective at delaying death from GVHD, compared to pre-transplant infusion or intravenous injection. Furthermore, we found that the dose of MSC was critical, as infusion of too few MSC was ineffective and infusion of too many MSC exacerbated the development of GVHD. Taken together, these results suggest that timing, dose and route of injection are all important factors to be considered to ensure successful therapeutic outcome. To investigate the in vivo mechanism of action, we conducted timed sacrifice experiments in the MHC-mismatched model to determine if MSC altered cytokine secretion and cellular effectors, such as DC, known to play a key role in GVHD. Despite the fact that MSC given post-HSCT enter an environment full of activated DC and IFNγ levels, by day 3 and 6 post infusion, these activated DC and IFNγ levels are decreased compared to controls or mice infused with MSC pre-transplant (p<0.05). This confirmed our in vitro data that IFNγ played an important role in MSC-mediated immunosuppression. In addition, when we removed a major source of IFNγ production in vivo by administering the T cell depleting antibody KT3 to mice with or without MSC, we found that although T cell depletion prolonged survival, MSC were unable to further enhance this effect. This was also true when MSC were used in combination with the conventional immunosuppressant cyclosporine. Finally, we examined whether the infusion of MSC would compromise the GVL effect. We found that whilst MSC could delay the onset of GVHD, in our model they did not alter the anti-tumour effects of the donor T cells. Overall, we have shown that MSC can delay but not prevent death from GVHD when administered at an appropriate time and dose and that IFNγ is required for MSC-mediated immunosuppression in our model. These data suggest that patients undergoing HSCT should be monitored for IFNγ, and administered MSC when high levels are reached. Whilst MSC may be a promising therapy for patients with severe GVHD, we highlight that further investigation is warranted before MSC are accepted for widespread use in the clinic. The risks and benefits for transplant recipients should be carefully considered before utilising MSC to treat or prevent GVHD.
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An investigation into the potential of mesenchymal stromal cells to attenuate graft-versus-host diseaseMelinda Elise Christensen Unknown Date (has links)
Survival of patients with poor prognosis or relapsed haematopoietic malignancies can be markedly improved by allogeneic haematopoietic stem cell transplantation (HSCT). HSCT reconstitutes the immune and haematopoietic systems after myeloablative conditioning and inhibits the recurrence of the malignancy by a graft-versus-leukaemia (GVL) response mediated by donor T cells. However, significant post-transplant complications such as graft-versus-host disease (GVHD) continue to plague the event-free survival of this curative procedure. GVHD is facilitated by donor T cells that recognise histocompatibility antigens on host antigen presenting cells (APC), such as dendritic cells (DC). Current treatment options for GVHD are focused on these T cells. However, these treatments result in an increased incidence of infection, graft rejection and relapse. A novel means of immunosuppression in GVHD is the use of multi-potent, mesenchymal stromal cells (MSC). MSC are non-immunogenic cells that actively suppress T cell function in vitro, and can resolve steroid-refractory GVHD in the clinic. Despite their use in the clinic, there is a paucity of pre-clinical data. Our aim was to investigate the in vivo efficacy of MSC to control GVHD while maintaining the beneficial GVL effect, and to begin to understand the mechanism by which MSC exert their immunosuppressive effects. We isolated and characterised MSC from murine bone/bone marrow and demonstrated that they suppressed T cell proliferation in vitro, even at low ratios of 1 MSC per 100 T cells. This was true of both donor-derived MSC, and MSC derived from unrelated donors (third party). Importantly, we observed that MSC significantly reduced T cell production of the pro-inflammatory cytokines TNFα and IFNγ in culture supernatants and that IFNγ plays a key role in the ability of MSC to suppress T cell proliferation. In vivo, we examined the effects of donor-derived MSC on GVHD severity and onset in two myeloablative murine models of HSCT. A major histocompatibility complex (MHC)-mismatched donor-recipient pair combination was used as a proof–of-principle model [UBI-GFP/BL6 (H-2b)àBALB/c (H-2d)], and an MHC-matched, minor histocompatibility antigen (miHA) mismatched donor-recipient pair combination was used to mimic MHC-matched sibling transplantation [UBI-GFP/BL6 (H-2b)àBALB.B (H-2b)]. We examined a number of variables related to MSC infusion including timing, dose and route of injection. We found that early post transplant infusion of MSC by the intraperitoneal injection was most effective at delaying death from GVHD, compared to pre-transplant infusion or intravenous injection. Furthermore, we found that the dose of MSC was critical, as infusion of too few MSC was ineffective and infusion of too many MSC exacerbated the development of GVHD. Taken together, these results suggest that timing, dose and route of injection are all important factors to be considered to ensure successful therapeutic outcome. To investigate the in vivo mechanism of action, we conducted timed sacrifice experiments in the MHC-mismatched model to determine if MSC altered cytokine secretion and cellular effectors, such as DC, known to play a key role in GVHD. Despite the fact that MSC given post-HSCT enter an environment full of activated DC and IFNγ levels, by day 3 and 6 post infusion, these activated DC and IFNγ levels are decreased compared to controls or mice infused with MSC pre-transplant (p<0.05). This confirmed our in vitro data that IFNγ played an important role in MSC-mediated immunosuppression. In addition, when we removed a major source of IFNγ production in vivo by administering the T cell depleting antibody KT3 to mice with or without MSC, we found that although T cell depletion prolonged survival, MSC were unable to further enhance this effect. This was also true when MSC were used in combination with the conventional immunosuppressant cyclosporine. Finally, we examined whether the infusion of MSC would compromise the GVL effect. We found that whilst MSC could delay the onset of GVHD, in our model they did not alter the anti-tumour effects of the donor T cells. Overall, we have shown that MSC can delay but not prevent death from GVHD when administered at an appropriate time and dose and that IFNγ is required for MSC-mediated immunosuppression in our model. These data suggest that patients undergoing HSCT should be monitored for IFNγ, and administered MSC when high levels are reached. Whilst MSC may be a promising therapy for patients with severe GVHD, we highlight that further investigation is warranted before MSC are accepted for widespread use in the clinic. The risks and benefits for transplant recipients should be carefully considered before utilising MSC to treat or prevent GVHD.
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An investigation into the potential of mesenchymal stromal cells to attenuate graft-versus-host diseaseMelinda Elise Christensen Unknown Date (has links)
Survival of patients with poor prognosis or relapsed haematopoietic malignancies can be markedly improved by allogeneic haematopoietic stem cell transplantation (HSCT). HSCT reconstitutes the immune and haematopoietic systems after myeloablative conditioning and inhibits the recurrence of the malignancy by a graft-versus-leukaemia (GVL) response mediated by donor T cells. However, significant post-transplant complications such as graft-versus-host disease (GVHD) continue to plague the event-free survival of this curative procedure. GVHD is facilitated by donor T cells that recognise histocompatibility antigens on host antigen presenting cells (APC), such as dendritic cells (DC). Current treatment options for GVHD are focused on these T cells. However, these treatments result in an increased incidence of infection, graft rejection and relapse. A novel means of immunosuppression in GVHD is the use of multi-potent, mesenchymal stromal cells (MSC). MSC are non-immunogenic cells that actively suppress T cell function in vitro, and can resolve steroid-refractory GVHD in the clinic. Despite their use in the clinic, there is a paucity of pre-clinical data. Our aim was to investigate the in vivo efficacy of MSC to control GVHD while maintaining the beneficial GVL effect, and to begin to understand the mechanism by which MSC exert their immunosuppressive effects. We isolated and characterised MSC from murine bone/bone marrow and demonstrated that they suppressed T cell proliferation in vitro, even at low ratios of 1 MSC per 100 T cells. This was true of both donor-derived MSC, and MSC derived from unrelated donors (third party). Importantly, we observed that MSC significantly reduced T cell production of the pro-inflammatory cytokines TNFα and IFNγ in culture supernatants and that IFNγ plays a key role in the ability of MSC to suppress T cell proliferation. In vivo, we examined the effects of donor-derived MSC on GVHD severity and onset in two myeloablative murine models of HSCT. A major histocompatibility complex (MHC)-mismatched donor-recipient pair combination was used as a proof–of-principle model [UBI-GFP/BL6 (H-2b)àBALB/c (H-2d)], and an MHC-matched, minor histocompatibility antigen (miHA) mismatched donor-recipient pair combination was used to mimic MHC-matched sibling transplantation [UBI-GFP/BL6 (H-2b)àBALB.B (H-2b)]. We examined a number of variables related to MSC infusion including timing, dose and route of injection. We found that early post transplant infusion of MSC by the intraperitoneal injection was most effective at delaying death from GVHD, compared to pre-transplant infusion or intravenous injection. Furthermore, we found that the dose of MSC was critical, as infusion of too few MSC was ineffective and infusion of too many MSC exacerbated the development of GVHD. Taken together, these results suggest that timing, dose and route of injection are all important factors to be considered to ensure successful therapeutic outcome. To investigate the in vivo mechanism of action, we conducted timed sacrifice experiments in the MHC-mismatched model to determine if MSC altered cytokine secretion and cellular effectors, such as DC, known to play a key role in GVHD. Despite the fact that MSC given post-HSCT enter an environment full of activated DC and IFNγ levels, by day 3 and 6 post infusion, these activated DC and IFNγ levels are decreased compared to controls or mice infused with MSC pre-transplant (p<0.05). This confirmed our in vitro data that IFNγ played an important role in MSC-mediated immunosuppression. In addition, when we removed a major source of IFNγ production in vivo by administering the T cell depleting antibody KT3 to mice with or without MSC, we found that although T cell depletion prolonged survival, MSC were unable to further enhance this effect. This was also true when MSC were used in combination with the conventional immunosuppressant cyclosporine. Finally, we examined whether the infusion of MSC would compromise the GVL effect. We found that whilst MSC could delay the onset of GVHD, in our model they did not alter the anti-tumour effects of the donor T cells. Overall, we have shown that MSC can delay but not prevent death from GVHD when administered at an appropriate time and dose and that IFNγ is required for MSC-mediated immunosuppression in our model. These data suggest that patients undergoing HSCT should be monitored for IFNγ, and administered MSC when high levels are reached. Whilst MSC may be a promising therapy for patients with severe GVHD, we highlight that further investigation is warranted before MSC are accepted for widespread use in the clinic. The risks and benefits for transplant recipients should be carefully considered before utilising MSC to treat or prevent GVHD.
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An investigation into the potential of mesenchymal stromal cells to attenuate graft-versus-host diseaseMelinda Elise Christensen Unknown Date (has links)
Survival of patients with poor prognosis or relapsed haematopoietic malignancies can be markedly improved by allogeneic haematopoietic stem cell transplantation (HSCT). HSCT reconstitutes the immune and haematopoietic systems after myeloablative conditioning and inhibits the recurrence of the malignancy by a graft-versus-leukaemia (GVL) response mediated by donor T cells. However, significant post-transplant complications such as graft-versus-host disease (GVHD) continue to plague the event-free survival of this curative procedure. GVHD is facilitated by donor T cells that recognise histocompatibility antigens on host antigen presenting cells (APC), such as dendritic cells (DC). Current treatment options for GVHD are focused on these T cells. However, these treatments result in an increased incidence of infection, graft rejection and relapse. A novel means of immunosuppression in GVHD is the use of multi-potent, mesenchymal stromal cells (MSC). MSC are non-immunogenic cells that actively suppress T cell function in vitro, and can resolve steroid-refractory GVHD in the clinic. Despite their use in the clinic, there is a paucity of pre-clinical data. Our aim was to investigate the in vivo efficacy of MSC to control GVHD while maintaining the beneficial GVL effect, and to begin to understand the mechanism by which MSC exert their immunosuppressive effects. We isolated and characterised MSC from murine bone/bone marrow and demonstrated that they suppressed T cell proliferation in vitro, even at low ratios of 1 MSC per 100 T cells. This was true of both donor-derived MSC, and MSC derived from unrelated donors (third party). Importantly, we observed that MSC significantly reduced T cell production of the pro-inflammatory cytokines TNFα and IFNγ in culture supernatants and that IFNγ plays a key role in the ability of MSC to suppress T cell proliferation. In vivo, we examined the effects of donor-derived MSC on GVHD severity and onset in two myeloablative murine models of HSCT. A major histocompatibility complex (MHC)-mismatched donor-recipient pair combination was used as a proof–of-principle model [UBI-GFP/BL6 (H-2b)àBALB/c (H-2d)], and an MHC-matched, minor histocompatibility antigen (miHA) mismatched donor-recipient pair combination was used to mimic MHC-matched sibling transplantation [UBI-GFP/BL6 (H-2b)àBALB.B (H-2b)]. We examined a number of variables related to MSC infusion including timing, dose and route of injection. We found that early post transplant infusion of MSC by the intraperitoneal injection was most effective at delaying death from GVHD, compared to pre-transplant infusion or intravenous injection. Furthermore, we found that the dose of MSC was critical, as infusion of too few MSC was ineffective and infusion of too many MSC exacerbated the development of GVHD. Taken together, these results suggest that timing, dose and route of injection are all important factors to be considered to ensure successful therapeutic outcome. To investigate the in vivo mechanism of action, we conducted timed sacrifice experiments in the MHC-mismatched model to determine if MSC altered cytokine secretion and cellular effectors, such as DC, known to play a key role in GVHD. Despite the fact that MSC given post-HSCT enter an environment full of activated DC and IFNγ levels, by day 3 and 6 post infusion, these activated DC and IFNγ levels are decreased compared to controls or mice infused with MSC pre-transplant (p<0.05). This confirmed our in vitro data that IFNγ played an important role in MSC-mediated immunosuppression. In addition, when we removed a major source of IFNγ production in vivo by administering the T cell depleting antibody KT3 to mice with or without MSC, we found that although T cell depletion prolonged survival, MSC were unable to further enhance this effect. This was also true when MSC were used in combination with the conventional immunosuppressant cyclosporine. Finally, we examined whether the infusion of MSC would compromise the GVL effect. We found that whilst MSC could delay the onset of GVHD, in our model they did not alter the anti-tumour effects of the donor T cells. Overall, we have shown that MSC can delay but not prevent death from GVHD when administered at an appropriate time and dose and that IFNγ is required for MSC-mediated immunosuppression in our model. These data suggest that patients undergoing HSCT should be monitored for IFNγ, and administered MSC when high levels are reached. Whilst MSC may be a promising therapy for patients with severe GVHD, we highlight that further investigation is warranted before MSC are accepted for widespread use in the clinic. The risks and benefits for transplant recipients should be carefully considered before utilising MSC to treat or prevent GVHD.
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Avaliação do potencial imunomodulador de células-tronco mesenquimais isoladas a partir de polpa dental, tecido adiposo e medula ósseaRodrigues, Felipe Valle Fortes January 2015 (has links)
Introdução: Células tronco mesenquimais (CTM) são uma população residente nos tecidos adultos de origem mesodérmica, com funções regenerativas de manutenção da integridade tecidual, com destaque no desempenho imunomodulador. Esse aspecto levou as CTM a tornarem-se ferramentas terapêuticas valiosas da pesquisa à assistência ao paciente em doenças autoimunes e de cunho inflamatório. Além disso, CTM podem ser isoladas de materiais tidos como descarte de procedimentos, como dentes decíduos, filtros de transplante de medula óssea e gordura. Nesse panorama, torna-se necessário estabelecer o efeito que a origem tecidual tem na eficiência imunoreguladora e na possível aplicabilidade clínica destas células. Objetivo: Comparar o potencial imunomodulador de células mesenquimais isoladas a partir de filtros descartados após a infusão de medula óssea, de lipoaspirado e de polpa de dentes decíduos. Métodos: Foi realizada a comparação da capacidade proliferativa de CTMs, cultivadas na presença de lisado plaquetário, das diversas fontes através do cálculo de population doubling das CTM em co-cultura com linfócitos T isolados em coluna magnética e com células mononucleares de sangue periférico, estimuladas com fitohemaglutinina; e determinado por citometria de fluxo o efeito das CTM das diversas fontes sobre as subpopulações linfocitárias. Resultados: CTM das três fontes foram capazes de inibir a proliferação de linfócitos e CTM de tecido adiposo foram mais eficientes em induzir o fenótipo de células T reguladoras e na diminuição de células T citotóxicas. Conclusão: comparadas à CTM isoladas de medula óssea e de polpa dentária, as CTM originadas de tecido adiposo exibem efeito imunomodulador mais acentuado. / Background: Mesenchymla stromal cells (MSC) reside in most adult tissue of mesenchymal origen, with a broad functions envolving cell repopulation and maintenence of tissue homeostasis, trough immunemmodulatory action. MSC are valuable terapêutic instruments applied from research to autoimune and inflamatory diseases. MSC can be isolated from diverse discarted biological matherials, like lipoaspirate, exfoliated deciduous teeeth and boné marrow ransplant filters. There so it´s necessary to stablish how source can impact MSC efficiency and possible clinical aplications. Objective: Compare immunomodulatory potential of adipose MSC and dental pulp MSC to boné marrow MSC. Methods: MSC from three selected sources were cocultured with phytohemaglutinin stimulated and magnetically isolated T cells and peripheral blood mononuclear cells; immunephenotype of cocultivated lymphocytes were also conducted. Results: MSC from all analyzed sources were capable to inhibit lymphocyte proliferation. Adipose MSC were capable to induce Treg phenotype and decrease T CD8+ limphocytes. Conclusion: Cell culture and therapy with MSC present many paradigms and we address to some of those to elucidate the possible most efficient source.
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Avaliação do potencial imunomodulador de células-tronco mesenquimais isoladas a partir de polpa dental, tecido adiposo e medula ósseaRodrigues, Felipe Valle Fortes January 2015 (has links)
Introdução: Células tronco mesenquimais (CTM) são uma população residente nos tecidos adultos de origem mesodérmica, com funções regenerativas de manutenção da integridade tecidual, com destaque no desempenho imunomodulador. Esse aspecto levou as CTM a tornarem-se ferramentas terapêuticas valiosas da pesquisa à assistência ao paciente em doenças autoimunes e de cunho inflamatório. Além disso, CTM podem ser isoladas de materiais tidos como descarte de procedimentos, como dentes decíduos, filtros de transplante de medula óssea e gordura. Nesse panorama, torna-se necessário estabelecer o efeito que a origem tecidual tem na eficiência imunoreguladora e na possível aplicabilidade clínica destas células. Objetivo: Comparar o potencial imunomodulador de células mesenquimais isoladas a partir de filtros descartados após a infusão de medula óssea, de lipoaspirado e de polpa de dentes decíduos. Métodos: Foi realizada a comparação da capacidade proliferativa de CTMs, cultivadas na presença de lisado plaquetário, das diversas fontes através do cálculo de population doubling das CTM em co-cultura com linfócitos T isolados em coluna magnética e com células mononucleares de sangue periférico, estimuladas com fitohemaglutinina; e determinado por citometria de fluxo o efeito das CTM das diversas fontes sobre as subpopulações linfocitárias. Resultados: CTM das três fontes foram capazes de inibir a proliferação de linfócitos e CTM de tecido adiposo foram mais eficientes em induzir o fenótipo de células T reguladoras e na diminuição de células T citotóxicas. Conclusão: comparadas à CTM isoladas de medula óssea e de polpa dentária, as CTM originadas de tecido adiposo exibem efeito imunomodulador mais acentuado. / Background: Mesenchymla stromal cells (MSC) reside in most adult tissue of mesenchymal origen, with a broad functions envolving cell repopulation and maintenence of tissue homeostasis, trough immunemmodulatory action. MSC are valuable terapêutic instruments applied from research to autoimune and inflamatory diseases. MSC can be isolated from diverse discarted biological matherials, like lipoaspirate, exfoliated deciduous teeeth and boné marrow ransplant filters. There so it´s necessary to stablish how source can impact MSC efficiency and possible clinical aplications. Objective: Compare immunomodulatory potential of adipose MSC and dental pulp MSC to boné marrow MSC. Methods: MSC from three selected sources were cocultured with phytohemaglutinin stimulated and magnetically isolated T cells and peripheral blood mononuclear cells; immunephenotype of cocultivated lymphocytes were also conducted. Results: MSC from all analyzed sources were capable to inhibit lymphocyte proliferation. Adipose MSC were capable to induce Treg phenotype and decrease T CD8+ limphocytes. Conclusion: Cell culture and therapy with MSC present many paradigms and we address to some of those to elucidate the possible most efficient source.
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Avaliação do potencial imunomodulador de células-tronco mesenquimais isoladas a partir de polpa dental, tecido adiposo e medula ósseaRodrigues, Felipe Valle Fortes January 2015 (has links)
Introdução: Células tronco mesenquimais (CTM) são uma população residente nos tecidos adultos de origem mesodérmica, com funções regenerativas de manutenção da integridade tecidual, com destaque no desempenho imunomodulador. Esse aspecto levou as CTM a tornarem-se ferramentas terapêuticas valiosas da pesquisa à assistência ao paciente em doenças autoimunes e de cunho inflamatório. Além disso, CTM podem ser isoladas de materiais tidos como descarte de procedimentos, como dentes decíduos, filtros de transplante de medula óssea e gordura. Nesse panorama, torna-se necessário estabelecer o efeito que a origem tecidual tem na eficiência imunoreguladora e na possível aplicabilidade clínica destas células. Objetivo: Comparar o potencial imunomodulador de células mesenquimais isoladas a partir de filtros descartados após a infusão de medula óssea, de lipoaspirado e de polpa de dentes decíduos. Métodos: Foi realizada a comparação da capacidade proliferativa de CTMs, cultivadas na presença de lisado plaquetário, das diversas fontes através do cálculo de population doubling das CTM em co-cultura com linfócitos T isolados em coluna magnética e com células mononucleares de sangue periférico, estimuladas com fitohemaglutinina; e determinado por citometria de fluxo o efeito das CTM das diversas fontes sobre as subpopulações linfocitárias. Resultados: CTM das três fontes foram capazes de inibir a proliferação de linfócitos e CTM de tecido adiposo foram mais eficientes em induzir o fenótipo de células T reguladoras e na diminuição de células T citotóxicas. Conclusão: comparadas à CTM isoladas de medula óssea e de polpa dentária, as CTM originadas de tecido adiposo exibem efeito imunomodulador mais acentuado. / Background: Mesenchymla stromal cells (MSC) reside in most adult tissue of mesenchymal origen, with a broad functions envolving cell repopulation and maintenence of tissue homeostasis, trough immunemmodulatory action. MSC are valuable terapêutic instruments applied from research to autoimune and inflamatory diseases. MSC can be isolated from diverse discarted biological matherials, like lipoaspirate, exfoliated deciduous teeeth and boné marrow ransplant filters. There so it´s necessary to stablish how source can impact MSC efficiency and possible clinical aplications. Objective: Compare immunomodulatory potential of adipose MSC and dental pulp MSC to boné marrow MSC. Methods: MSC from three selected sources were cocultured with phytohemaglutinin stimulated and magnetically isolated T cells and peripheral blood mononuclear cells; immunephenotype of cocultivated lymphocytes were also conducted. Results: MSC from all analyzed sources were capable to inhibit lymphocyte proliferation. Adipose MSC were capable to induce Treg phenotype and decrease T CD8+ limphocytes. Conclusion: Cell culture and therapy with MSC present many paradigms and we address to some of those to elucidate the possible most efficient source.
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