OBJECTIVE： To assess the effect of human biofield therapy, an integrative medicine modality, on the development of tumors and metastasis, and immune function in a mouse breast cancer model. METHODS： Mice were inject...OBJECTIVE： To assess the effect of human biofield therapy, an integrative medicine modality, on the development of tumors and metastasis, and immune function in a mouse breast cancer model. METHODS： Mice were injected with 66cl4 mammary carcinoma cells. In study one, mice received biofield therapy after cell injection. In study two, mice were treated by the biofield practitioner only prior to cell injection. Both studies had two control groups of mock biofield treatments and phosphate- buffered saline injection. Mice were weighed and tumor volume was determined. Blood samples were collected and 32 serum cytokine/chemokine markers were measured. Spleens/popliteal lymph nodes were isolated and dissociated for fluorescent-activated cell sorting （FACS） analysis of immune cells or metastasis assays in cell culture. RESULTS： No signifcant differences were found in weight, tumor size or metastasis. Significant effects were found in the immune responses in study one but no additional effects were found in study two. In study one, human biofield treatment significantly reduced percentage of CD4~CD441oCD25~ and percentage of CD8~ cells, elevated by cancer in the lymph nodes, to control levels determined by FACS analysis. In the spleen, only CD11b~ macrophages were increased with cancer, and human biofield therapy significantly reduced them. Of 11 cytokines elevated by cancer, only interferon-y, interleukin-1, monokine induced by interferon-y, interleukin-2 and macrophage inflammatory protein-2 were significantly reduced to control levels with human biofield therapy. CONCLUSION： Human biofield therapy had no significant effect on tumor size or metastasis but produced significant effects on immune responses apparent in the down-regulation of specific lymphocytes and serum cytokines in a mouse breast cancer model.展开更多
We have previously developed a poly(L-lactic)acid(PLLA)bioengineered anterior cruciate ligament(ACL)matrix that has demonstrated enhanced healing when seeded with primary ACL cells prior to implantation in a rabbit mo...We have previously developed a poly(L-lactic)acid(PLLA)bioengineered anterior cruciate ligament(ACL)matrix that has demonstrated enhanced healing when seeded with primary ACL cells prior to implantation in a rabbit model,as compared with the matrix alone.This suggests that improving cell adhesion on the matrix may beneficially affect the healing response and long-term performance of the bioengineered ACL matrix.One regenerative engineering approach involves enhancing the surface properties of the matrix to support cell adhesion and growth in combination with point-of-care stem cell therapy.Herein,we studied the cell adhesion properties of PLLA braided microfiber matrices enhanced through the physical adsorption of fibronectin and air plasma treatment.We evaluated the kinetics and binding efficiency of fibronectin onto matrices at three time points and three fibronectin concentrations.Incubating the matrix for 120 min in a solution of 25 lgmL1 fibronectin achieved the greatest binding efficiency to the matrix and cellular adhesion.Exposing the matrices to air plasma treatment for 5 min before fibronectin adsorption significantly enhanced the cell adhesion of rabbit bone marrow-derived mesenchymal stem cells(R-BMMSCs)24 h post cell seeding.Finally,cellular proliferation was monitored for up to 21 d,the matrices were exposed to air plasma treatment,and fibronectin adsorption was found to result in enhanced cell number.These findings suggest that exposure to air plasma treatment and fibronectin adsorption enhances the cellular adhesion of PLLA braided microfiber matrices and may improve the clinical efficacy of the matrix in combination with point-of-care stem cell therapies.展开更多
Tendon and ligament injuries are the most common musculoskeletal injuries,which not only impact the quality of life but result in a massive economic burden.Surgical interventions for tendon/ligament injuries utilize b...Tendon and ligament injuries are the most common musculoskeletal injuries,which not only impact the quality of life but result in a massive economic burden.Surgical interventions for tendon/ligament injuries utilize biological and/or engineered grafts to reconstruct damaged tissue,but these have limitations.Engineered matrices confer superior physicochemical properties over biological grafts but lack desirable bioactivity to promote tissue healing.While incorporating drugs can enhance bioactivity,large matrix surface areas and hydrophobicity can lead to uncontrolled burst release and/or incomplete release due to binding.To overcome these limitations,we evaluated the delivery of a peptide growth factor(exendin-4;Ex-4)using an enhanced nanofiber matrix in a tendon injury model.To overcome drug surface binding due to matrix hydrophobicity of poly(caprolactone)(PCL)-which would be expected to enhance cell-material interactions-we blended PCL and cellulose acetate(CA)and electrospun nanofiber matrices with fiber diameters ranging from 600 to 1000 nm.To avoid burst release and protect the drug,we encapsulated Ex-4 in the open lumen of halloysite nanotubes(HNTs),sealed the HNT tube endings with a polymer blend,and mixed Ex-4-loaded HNTs into the polymer mixture before electrospinning.This reduced burst release from~75%to~40%,but did not alter matrix morphology,fiber diameter,or tensile properties.We evaluated the bioactivity of the Ex-4 nanofiber formulation by culturing human mesenchymal stem cells(hMSCs)on matrix surfaces for 21 days and measuring tenogenic differentiation,compared with nanofiber matrices in basal media alone.Strikingly,we observed that Ex-4 nanofiber matrices accelerated the hMSC proliferation rate and elevated levels of sulfated glycosaminoglycan,tendon-related genes(Scx,Mkx,and Tnmd),and ECM-related genes(Col-Ⅰ,Col-Ⅲ,and Dcn),compared to control.We then assessed the safety and efficacy of Ex-4 nanofiber matrices in a full-thickness rat Achilles tendon defect with histology,marker expression,functional walking track analysis,and mechanical testing.Our analysis confirmed that Ex-4 nanofiber matrices enhanced tendon healing and reduced fibrocartilage formation versus nanofiber matrices alone.These findings implicate Ex-4 as a potentially valuable tool for tendon tissue engineering.展开更多
基金the Trivedi Foundation for funding this research
文摘OBJECTIVE： To assess the effect of human biofield therapy, an integrative medicine modality, on the development of tumors and metastasis, and immune function in a mouse breast cancer model. METHODS： Mice were injected with 66cl4 mammary carcinoma cells. In study one, mice received biofield therapy after cell injection. In study two, mice were treated by the biofield practitioner only prior to cell injection. Both studies had two control groups of mock biofield treatments and phosphate- buffered saline injection. Mice were weighed and tumor volume was determined. Blood samples were collected and 32 serum cytokine/chemokine markers were measured. Spleens/popliteal lymph nodes were isolated and dissociated for fluorescent-activated cell sorting （FACS） analysis of immune cells or metastasis assays in cell culture. RESULTS： No signifcant differences were found in weight, tumor size or metastasis. Significant effects were found in the immune responses in study one but no additional effects were found in study two. In study one, human biofield treatment significantly reduced percentage of CD4~CD441oCD25~ and percentage of CD8~ cells, elevated by cancer in the lymph nodes, to control levels determined by FACS analysis. In the spleen, only CD11b~ macrophages were increased with cancer, and human biofield therapy significantly reduced them. Of 11 cytokines elevated by cancer, only interferon-y, interleukin-1, monokine induced by interferon-y, interleukin-2 and macrophage inflammatory protein-2 were significantly reduced to control levels with human biofield therapy. CONCLUSION： Human biofield therapy had no significant effect on tumor size or metastasis but produced significant effects on immune responses apparent in the down-regulation of specific lymphocytes and serum cytokines in a mouse breast cancer model.
基金This research was supported by funding from the Raymond and Beverly Sackler Center for Biomedical,Biological,Physical and Engineering Sciences(NIH R01AR063698,NIH R01AR063698-02S1,and NIH DP1 AR068147).
文摘We have previously developed a poly(L-lactic)acid(PLLA)bioengineered anterior cruciate ligament(ACL)matrix that has demonstrated enhanced healing when seeded with primary ACL cells prior to implantation in a rabbit model,as compared with the matrix alone.This suggests that improving cell adhesion on the matrix may beneficially affect the healing response and long-term performance of the bioengineered ACL matrix.One regenerative engineering approach involves enhancing the surface properties of the matrix to support cell adhesion and growth in combination with point-of-care stem cell therapy.Herein,we studied the cell adhesion properties of PLLA braided microfiber matrices enhanced through the physical adsorption of fibronectin and air plasma treatment.We evaluated the kinetics and binding efficiency of fibronectin onto matrices at three time points and three fibronectin concentrations.Incubating the matrix for 120 min in a solution of 25 lgmL1 fibronectin achieved the greatest binding efficiency to the matrix and cellular adhesion.Exposing the matrices to air plasma treatment for 5 min before fibronectin adsorption significantly enhanced the cell adhesion of rabbit bone marrow-derived mesenchymal stem cells(R-BMMSCs)24 h post cell seeding.Finally,cellular proliferation was monitored for up to 21 d,the matrices were exposed to air plasma treatment,and fibronectin adsorption was found to result in enhanced cell number.These findings suggest that exposure to air plasma treatment and fibronectin adsorption enhances the cellular adhesion of PLLA braided microfiber matrices and may improve the clinical efficacy of the matrix in combination with point-of-care stem cell therapies.
文摘Tendon and ligament injuries are the most common musculoskeletal injuries,which not only impact the quality of life but result in a massive economic burden.Surgical interventions for tendon/ligament injuries utilize biological and/or engineered grafts to reconstruct damaged tissue,but these have limitations.Engineered matrices confer superior physicochemical properties over biological grafts but lack desirable bioactivity to promote tissue healing.While incorporating drugs can enhance bioactivity,large matrix surface areas and hydrophobicity can lead to uncontrolled burst release and/or incomplete release due to binding.To overcome these limitations,we evaluated the delivery of a peptide growth factor(exendin-4;Ex-4)using an enhanced nanofiber matrix in a tendon injury model.To overcome drug surface binding due to matrix hydrophobicity of poly(caprolactone)(PCL)-which would be expected to enhance cell-material interactions-we blended PCL and cellulose acetate(CA)and electrospun nanofiber matrices with fiber diameters ranging from 600 to 1000 nm.To avoid burst release and protect the drug,we encapsulated Ex-4 in the open lumen of halloysite nanotubes(HNTs),sealed the HNT tube endings with a polymer blend,and mixed Ex-4-loaded HNTs into the polymer mixture before electrospinning.This reduced burst release from~75%to~40%,but did not alter matrix morphology,fiber diameter,or tensile properties.We evaluated the bioactivity of the Ex-4 nanofiber formulation by culturing human mesenchymal stem cells(hMSCs)on matrix surfaces for 21 days and measuring tenogenic differentiation,compared with nanofiber matrices in basal media alone.Strikingly,we observed that Ex-4 nanofiber matrices accelerated the hMSC proliferation rate and elevated levels of sulfated glycosaminoglycan,tendon-related genes(Scx,Mkx,and Tnmd),and ECM-related genes(Col-Ⅰ,Col-Ⅲ,and Dcn),compared to control.We then assessed the safety and efficacy of Ex-4 nanofiber matrices in a full-thickness rat Achilles tendon defect with histology,marker expression,functional walking track analysis,and mechanical testing.Our analysis confirmed that Ex-4 nanofiber matrices enhanced tendon healing and reduced fibrocartilage formation versus nanofiber matrices alone.These findings implicate Ex-4 as a potentially valuable tool for tendon tissue engineering.
