Auto-HCT versus Allo-HCT for T-Cell Lymphoma. Conclusion: In this limited set of patients with T-... more Auto-HCT versus Allo-HCT for T-Cell Lymphoma. Conclusion: In this limited set of patients with T-Cell malignancy and in a subset with T-Cell Lymphoma, overall survival after autologous and allogeneic HCT appears equivalent to published series utilizing conventional conditioning regimens. We conclude that FBT might offer certain patients an alternative conditioning regimen whose co-morbid status places them at risk for TRM from conventional regimens.
The aim of this study was to investigate the effects of percutaneous transplanted autologous neur... more The aim of this study was to investigate the effects of percutaneous transplanted autologous neurogenically-induced bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to external spinal trauma. Thirteen client owned dogs that had failed in improvement neurologically at least 42 days after conservative management, decompression and decompression-stabilization were included in the study. Each dog received two doses of autologous 5.0 × 10 6 NIBM-MSCs suspension, which were positive to 2′,3′-Cyclic-nucleotide-3′-phosphodiesterase (CNPase) and Microtubule-associated protein 2 (MAP-2), as well as to Glial fibrillary acidic protein (GFAP) and beta III tubulin. The cells were injected into the spinal cord through the hemilaminectomy or laminectomy defects percutaneously with 21 days interval for 2 times. The results were evaluated using Texas Spinal Cord Injury Scale (TSCIS), somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) at the admission time, cell transplantation procedures and during 2, 5, 7 and 12th months after the second cell transplantation. Improvement after cell transplantation in gait, nociception, proprioception, SEP and MEP results was observed in just 2 cases, and only gait score improvement was seen in 6 cases, and no improvement was recorded in 5 cases. All progresses were observed until 2nd month after the second cell transplantation, however, there was no improvement after this period. In conclusion, percutaneous transplantation of autologous NIBM-MSCs is a promising candidate modality for cases with spinal cord injury after spinal trauma and poor prognosis.
Tissue engineering and cell therapy have been presented as optional treatment modalities for foca... more Tissue engineering and cell therapy have been presented as optional treatment modalities for focal lesions of articular cartilage. The consequence can vary between a fibrous tissue and a hyaline-like neocartilage. Studies have approved the use of a hydrogel matrix substrate, chondrogenic medium, and a dynamic culture system for developing an articular cartilage tissue to constitute the native-like ECM composition. The objective of this in vitro study was to develop a rat hyaline-like cartilage by culturing articular chondrocytes encapsulated in calcium alginate fibers, under the influence of a microgravity bioreactor inside chondrogenic medium. Our results demonstrated that chondrocytes encapsulated in calcium alginate fibers had higher extracellular matrix production compared with that of calcium alginate beads. The data also suggest that calcium alginate fibers inside rotating bioreactor provides an environment that mediates isolated rat chondrocytes to redifferentiate and form hy...
Polycaprolactone porous membranes were obtained by freeze extraction of dioxane from polycaprolac... more Polycaprolactone porous membranes were obtained by freeze extraction of dioxane from polycaprolactone-dioxane solid solutions. Porosities as high as 90% with interconnected structures were obtained by this technique. A silica phase was synthesized inside the pores of the polymer membrane by sol-gel reaction using tetraethylorthosilicate (TEOS) as a silica precursor and catalyzed in acidic and basic conditions. Two different morphologies of the inorganic phase were obtained depending on the type of catalyst. In acid catalyzed sol-gel reaction, a homogeneous layer of silica was deposited on the pores, and discrete microspheres were synthesized on the pore walls when a basic catalyst was used. The morphology of the inorganic phase influenced the mechanical and thermal behavior, as well as the hydrophilic character of the composites. Bioactivity of the porous materials was tested in vitro by measuring the deposition of hydroxyapatite on the surfaces of the porous composite membranes. Polycaprolactone/silica composites revealed a superior bioactivity performance compared with that of the pure polymer; evidenced by the characteristic cauliflower structures on the material surface, increase in weight and Ca/P ratio of the hydroxyapatite layer. Also, the acid catalyzed composites presented better bioactivity than the base catalyzed composites, evidencing the importance in the morphology of the silica phase.
In this study, the osteogenic potential of rat bone marrow mesenchymal stem cells (rBM-MSCs) on a... more In this study, the osteogenic potential of rat bone marrow mesenchymal stem cells (rBM-MSCs) on a biomimetic poly(e-caprolactone)/b-tricalcium phosphate (PCL/b-TCP) composite scaffold composed of parallel concentric fibrous membranes was evaluated in vitro and in vivo. PCL/b-TCP composite membranes were prepared by electrospinning and characterized by x-ray diffraction, differential scanning calorimetry, Fourier transform-infrared spectroscopy, and scanning electron microscopy (SEM). rBM-MSCs were seeded on three-dimensional multispiral scaffolds prepared by the assembly of composite membranes. The cell-scaffold constructs were cultured in osteogenic medium for 4 weeks. Histochemical studies and biochemical assays confirmed the osteogenic differentiation of rBM-MSCs inside the scaffold by documenting the dense mineralized extracellular matrix formation starting from the second week of culture. In the in vivo part of the study, cellscaffold constructs precultured for 7 days were implanted subcutaneously into the epigastric groin fascia of Wistar rats for a duration of 6 months. Ectopic bone-tissue like formation was documented by using computerized tomography, confocal laser microscopy, SEM, and histochemistry. In vivo findings indicated that the biomimetic multispiral scaffold seeded with rBM-MSCs supports the ectopic formation of new bone tissue in Wistar rats. V
The goal of this study was to develop an injectable form of decellularized bovine myocardial tiss... more The goal of this study was to develop an injectable form of decellularized bovine myocardial tissue matrix which could retain high levels of functional ECM molecules, and could gel at physiological temperature. Dissected ventricular tissue was processed by a detergent-based protocol, lyophilized, enzymatically-digested, and neutralized to form the injectable myocardial matrix (IMM). Histochemical analysis, DNA quantification, and agarose gel electrophoresis demonstrated the efficiency of the applied protocol. Chemical, thermal, morphological, and rheological characterization; protein and sulfated glycosaminoglycan (sGAG) content analysis were performed, in vitro biological properties were evaluated. An in vivo histocompatibility and biodegradability study was performed. Histochemistry revealed complete removal of myocardial cells. DNA content analysis revealed a significant decrease (87%) in the nuclear material, while protein and sGAG contents were highly preserved following decell...
Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenera... more Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have been widely investigated in preclinical and clinical studies for therapeutic purposes. Extracellular vesicles (EVs) are the vital mediators that regulate the therapeutic effects of stem cells. Besides, they carry various types of cargo between cells which make them a significant contributor of intercellular communication. Given their role in physiological and pathological conditions in living cells, EVs are considered as a new therapeutic alternative solution for a variety of diseases in which there is a high unmet clinical need. This review aims to summarize and identify therapeutic potential of stem cells and EVs in diseases requiring acute emergency care such as trauma, heart diseases, stroke, acute respiratory distress syndrome and burn injury. Diseases that affect militaries or societies including acute radiation syndrome, sepsis and viral pandemics such as novel coronavirus disease 2019 are also discussed. Additionally, featuring and problematic issues that hamper clinical translation of stem cells and EVs are debated in a comparative manner with a futuristic perspective.
Auto-HCT versus Allo-HCT for T-Cell Lymphoma. Conclusion: In this limited set of patients with T-... more Auto-HCT versus Allo-HCT for T-Cell Lymphoma. Conclusion: In this limited set of patients with T-Cell malignancy and in a subset with T-Cell Lymphoma, overall survival after autologous and allogeneic HCT appears equivalent to published series utilizing conventional conditioning regimens. We conclude that FBT might offer certain patients an alternative conditioning regimen whose co-morbid status places them at risk for TRM from conventional regimens.
The aim of this study was to investigate the effects of percutaneous transplanted autologous neur... more The aim of this study was to investigate the effects of percutaneous transplanted autologous neurogenically-induced bone marrow-derived mesenchymal stem cells (NIBM-MSCs) in paraplegic dogs without deep pain perception (DPP) secondary to external spinal trauma. Thirteen client owned dogs that had failed in improvement neurologically at least 42 days after conservative management, decompression and decompression-stabilization were included in the study. Each dog received two doses of autologous 5.0 × 10 6 NIBM-MSCs suspension, which were positive to 2′,3′-Cyclic-nucleotide-3′-phosphodiesterase (CNPase) and Microtubule-associated protein 2 (MAP-2), as well as to Glial fibrillary acidic protein (GFAP) and beta III tubulin. The cells were injected into the spinal cord through the hemilaminectomy or laminectomy defects percutaneously with 21 days interval for 2 times. The results were evaluated using Texas Spinal Cord Injury Scale (TSCIS), somatosensory evoked potentials (SEP) and motor evoked potentials (MEP) at the admission time, cell transplantation procedures and during 2, 5, 7 and 12th months after the second cell transplantation. Improvement after cell transplantation in gait, nociception, proprioception, SEP and MEP results was observed in just 2 cases, and only gait score improvement was seen in 6 cases, and no improvement was recorded in 5 cases. All progresses were observed until 2nd month after the second cell transplantation, however, there was no improvement after this period. In conclusion, percutaneous transplantation of autologous NIBM-MSCs is a promising candidate modality for cases with spinal cord injury after spinal trauma and poor prognosis.
Tissue engineering and cell therapy have been presented as optional treatment modalities for foca... more Tissue engineering and cell therapy have been presented as optional treatment modalities for focal lesions of articular cartilage. The consequence can vary between a fibrous tissue and a hyaline-like neocartilage. Studies have approved the use of a hydrogel matrix substrate, chondrogenic medium, and a dynamic culture system for developing an articular cartilage tissue to constitute the native-like ECM composition. The objective of this in vitro study was to develop a rat hyaline-like cartilage by culturing articular chondrocytes encapsulated in calcium alginate fibers, under the influence of a microgravity bioreactor inside chondrogenic medium. Our results demonstrated that chondrocytes encapsulated in calcium alginate fibers had higher extracellular matrix production compared with that of calcium alginate beads. The data also suggest that calcium alginate fibers inside rotating bioreactor provides an environment that mediates isolated rat chondrocytes to redifferentiate and form hy...
Polycaprolactone porous membranes were obtained by freeze extraction of dioxane from polycaprolac... more Polycaprolactone porous membranes were obtained by freeze extraction of dioxane from polycaprolactone-dioxane solid solutions. Porosities as high as 90% with interconnected structures were obtained by this technique. A silica phase was synthesized inside the pores of the polymer membrane by sol-gel reaction using tetraethylorthosilicate (TEOS) as a silica precursor and catalyzed in acidic and basic conditions. Two different morphologies of the inorganic phase were obtained depending on the type of catalyst. In acid catalyzed sol-gel reaction, a homogeneous layer of silica was deposited on the pores, and discrete microspheres were synthesized on the pore walls when a basic catalyst was used. The morphology of the inorganic phase influenced the mechanical and thermal behavior, as well as the hydrophilic character of the composites. Bioactivity of the porous materials was tested in vitro by measuring the deposition of hydroxyapatite on the surfaces of the porous composite membranes. Polycaprolactone/silica composites revealed a superior bioactivity performance compared with that of the pure polymer; evidenced by the characteristic cauliflower structures on the material surface, increase in weight and Ca/P ratio of the hydroxyapatite layer. Also, the acid catalyzed composites presented better bioactivity than the base catalyzed composites, evidencing the importance in the morphology of the silica phase.
In this study, the osteogenic potential of rat bone marrow mesenchymal stem cells (rBM-MSCs) on a... more In this study, the osteogenic potential of rat bone marrow mesenchymal stem cells (rBM-MSCs) on a biomimetic poly(e-caprolactone)/b-tricalcium phosphate (PCL/b-TCP) composite scaffold composed of parallel concentric fibrous membranes was evaluated in vitro and in vivo. PCL/b-TCP composite membranes were prepared by electrospinning and characterized by x-ray diffraction, differential scanning calorimetry, Fourier transform-infrared spectroscopy, and scanning electron microscopy (SEM). rBM-MSCs were seeded on three-dimensional multispiral scaffolds prepared by the assembly of composite membranes. The cell-scaffold constructs were cultured in osteogenic medium for 4 weeks. Histochemical studies and biochemical assays confirmed the osteogenic differentiation of rBM-MSCs inside the scaffold by documenting the dense mineralized extracellular matrix formation starting from the second week of culture. In the in vivo part of the study, cellscaffold constructs precultured for 7 days were implanted subcutaneously into the epigastric groin fascia of Wistar rats for a duration of 6 months. Ectopic bone-tissue like formation was documented by using computerized tomography, confocal laser microscopy, SEM, and histochemistry. In vivo findings indicated that the biomimetic multispiral scaffold seeded with rBM-MSCs supports the ectopic formation of new bone tissue in Wistar rats. V
The goal of this study was to develop an injectable form of decellularized bovine myocardial tiss... more The goal of this study was to develop an injectable form of decellularized bovine myocardial tissue matrix which could retain high levels of functional ECM molecules, and could gel at physiological temperature. Dissected ventricular tissue was processed by a detergent-based protocol, lyophilized, enzymatically-digested, and neutralized to form the injectable myocardial matrix (IMM). Histochemical analysis, DNA quantification, and agarose gel electrophoresis demonstrated the efficiency of the applied protocol. Chemical, thermal, morphological, and rheological characterization; protein and sulfated glycosaminoglycan (sGAG) content analysis were performed, in vitro biological properties were evaluated. An in vivo histocompatibility and biodegradability study was performed. Histochemistry revealed complete removal of myocardial cells. DNA content analysis revealed a significant decrease (87%) in the nuclear material, while protein and sGAG contents were highly preserved following decell...
Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenera... more Regenerative medicine (RM) is an interdisciplinary field that aims to repair, replace or regenerate damaged or missing tissue or organs to function as close as possible to its physiological architecture and functions. Stem cells, which are undifferentiated cells retaining self-renewal potential, excessive proliferation and differentiation capacity into offspring or daughter cells that form different lineage cells of an organism, are considered as an important part of the RM approaches. They have been widely investigated in preclinical and clinical studies for therapeutic purposes. Extracellular vesicles (EVs) are the vital mediators that regulate the therapeutic effects of stem cells. Besides, they carry various types of cargo between cells which make them a significant contributor of intercellular communication. Given their role in physiological and pathological conditions in living cells, EVs are considered as a new therapeutic alternative solution for a variety of diseases in which there is a high unmet clinical need. This review aims to summarize and identify therapeutic potential of stem cells and EVs in diseases requiring acute emergency care such as trauma, heart diseases, stroke, acute respiratory distress syndrome and burn injury. Diseases that affect militaries or societies including acute radiation syndrome, sepsis and viral pandemics such as novel coronavirus disease 2019 are also discussed. Additionally, featuring and problematic issues that hamper clinical translation of stem cells and EVs are debated in a comparative manner with a futuristic perspective.
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