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Papers by Raphael Gorodetsky
International Journal of Molecular Sciences, 2021
The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow... more The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of reje...
Stem Cells Translational Medicine, 2019
Osteoarthritic and other types of articular cartilage defects never heal on their own. Medicinal ... more Osteoarthritic and other types of articular cartilage defects never heal on their own. Medicinal and surgical approaches are often ineffective, and the supply of autologous chondrocytes for tissue engineering is very limited. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) have been suggested as an adequate cell source for cartilage reconstruction. However, the majority of studies employing BMSCs for cartilage tissue engineering have used BMSCs predifferentiated into cartilage prior to implantation. This strategy has failed to achieve formation of stable, hyaline-like cartilage, resistant to hypertrophy in vivo. We hypothesized that in vitro predifferentiation of BMSCs is not necessary when cells are combined with an adequate scaffold that supports the formation of stable cartilage in vivo. In this study, naïve (undifferentiated) human BMSCs were attached to dehydrothermally crosslinked stable fibrin microbeads (FMBs) without and with othe...
Critical Reviews in Oncology/Hematology, 2017
Melanoma is a highly lethal cancer deriving from transformed dermal melanocytes. Early diagnosed ... more Melanoma is a highly lethal cancer deriving from transformed dermal melanocytes. Early diagnosed primary melanoma may be curable, but the cure-rate of more advanced stages is limited, with high mortality rate. With the progression of the tumor, the melanocytes overexpress intracellular or cell-surface molecules, including ectopic normal and tumor-specific proteins. Some of these induce a specific immune response by T and B lymphocytes. Antibodies raised against melanoma antigens were proposed for differential disease diagnosis, staging, prognosis and evaluation of treatment efficiency. Nevertheless, treatments based on stimulation of specific antimelanoma immune responses have had only limited success. It seems that efficient immunotherapy should become more feasible pending on finding new adequate antigens to target. New insights into immune regulation of the tumor microenvironment and its progression may help the development of more successful treatments. We present here up-to-date information on known major melanoma-associated antigens, which could serve as tools for diagnosis as well as for clinical immunotherapy. This approach with promising results for treating some other selected malignancies is still experimental with a very limited success in melanoma. The development of new immune modulators of the tumor microenvironment and neo-antigens may be additional promising directions and may open new opportunities for the immunotherapy of melanoma.
Journal of Vascular Research, 2010
Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/jvr_issues 108 Antioxidants Reverse Age-Related Collateral Growth Impairment
International Journal of Dermatology, 1986
The concentrations of zinc (Zn), copper (Cu), and iron (Fe) in the skin have been noninvasively d... more The concentrations of zinc (Zn), copper (Cu), and iron (Fe) in the skin have been noninvasively determined in vivo by diagnostic x-ray spectrometry. The skin of healthy controls was divided into two major groups based upon the distribution of the concentrations of these elements. In the face and upper neck, the following wet weight concentrations were recorded: Fe, 14.2 +/- 3.3 ppm; Cu, 1.3 +/- 0.3 ppm; and Zn, 6.7 +/- 1.1 ppm. In the chest, abdomen, arm, axilla, and lower neck, the concentrations of these elements were as follows: Fe, 10.2 +/- 2.5 ppm; Cu, 0.8 +/- 0.3 ppm; and Zn, 4.5 +/- 1.7 ppm. In most lesions of solar dermatitis, solar keratosis, basal and squamous cell carcinomas, variable elevations of Zn and Fe (up to significant levels) were recorded in most of the contralateral, apparently uninvolved skin. In the majority of pigmented nevi and malignant melanomas, the levels of Fe and Zn were elevated. In some of these, the Cu concentration also was increased.
Zeitschrift für Parasitenkunde
ABSTRACT
Journal of Neuroimmunology, 2014
Cancer immunology, immunotherapy : CII, Jan 2, 2015
Targeted cancer immunotherapy is challenging due to the cellular diversity and imposed immune tol... more Targeted cancer immunotherapy is challenging due to the cellular diversity and imposed immune tolerance in the tumor microenvironment (TME). A promising route to overcome those drawbacks may be by activating innate immune cells (IIC) in the TME, toward tumor destruction. Studies have shown the ability to "re-educate" pro-tumor-activated IIC toward antitumor responses. The current research aims to stimulate such activation using a combination of innate activators loaded onto microparticles (MP). Four inducers of Toll-like receptors 4 and 7, complement C5a receptor (C5aR) and gamma Fc receptor and their combinations were loaded on MP, and their influence on immune cell activation evaluated. MP stimulation of immune cell activation was tested in vitro and in vivo using a subcutaneous B16-F10 melanoma model induced in C57BL6 mice. Exposure to the TLR4 ligand lipopolysaccharide (LPS) bound to MP-induced acute inflammatory cytokine and chemokine activity in vitro and in vivo, wi...
... 3,4 Moreover, the microenvironment substantially contributes to tumor escape by:5 limiting th... more ... 3,4 Moreover, the microenvironment substantially contributes to tumor escape by:5 limiting the action of the immune system; counteracting the performance of chemotherapeutic agents; Stem Cell-Based Tissue Repair Edited by Raphael Gorodetsky and Richard Schafer r The ...
Vaccine, 2007
Transcutaneous immunization aims at taking advantage of the skin's immune system for the purpose ... more Transcutaneous immunization aims at taking advantage of the skin's immune system for the purpose of immunoprotection. In the present study we evaluated the potential of topical delivery of a recombinant melanoma protein, HR-gp100, derived from a shorter sequence of the native gp100 gene. The protein was applied on the skin, with and without the addition of two forms of heat labile enterotoxin (nLT and LTB). HR-gp100 fused to Haptide, a cell penetrating 20mer peptide (HR-gp100H) was also tested. Topical HR-gp100 and HR-gp100H application on the ears of mice elicited the production of specific antibodies, and transcutaneous delivery to intact human skin induced dosedependent LC activation. nLT and LTB also activated LC, but did not further increase the activation induced by HR-gp100. These results show that HR-gp100, an antigenic tumor-derived protein, activates the immune system following transcutaneous delivery, as shown by both Langerhans cell activation and induction of antibody production.
Radiation Research, 1991
ABSTRACT
Nous avons developpe de nouvelles microbilles en fibrine (MBF) biodegradables, de 50 a 300 mm de ... more Nous avons developpe de nouvelles microbilles en fibrine (MBF) biodegradables, de 50 a 300 mm de diametre, pour servir de puissants vecteurs cellulaires. Les MBF se sont revelees haptotactiques vis-a-vis d'un vaste eventail de types cellulaires. Il s'agit notamment de cellules normales telles que les cellules primaires endotheliales, les cellules musculaires lisses, les fibroblastes, les chondrocytes et les osteoblastes, les progeniteurs osteogeniques de la moelle osseuse, ainsi que plusieurs cellules transformees, telles que les 3T3 et les lignees cellulaires de carcinome mammaire de souris. Les MBF ont fixe de maniere minimale les keratinocytes et differentes lignees cellulaires de la serie leucocytaire. Les cellules ont pu etre maintenues sur les MBF a des densites extremement elevees pendant plus de 2 semaines et elles ont pu etre transferees dans des tubes a ensemencer ou dechargees sans trypsination prealable. La microscopie optique, a fluorescence et laser confocale a...
International Journal of Molecular Sciences, 2021
The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow... more The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow (BM, bmMSCs), adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of reje...
Stem Cells Translational Medicine, 2019
Osteoarthritic and other types of articular cartilage defects never heal on their own. Medicinal ... more Osteoarthritic and other types of articular cartilage defects never heal on their own. Medicinal and surgical approaches are often ineffective, and the supply of autologous chondrocytes for tissue engineering is very limited. Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) have been suggested as an adequate cell source for cartilage reconstruction. However, the majority of studies employing BMSCs for cartilage tissue engineering have used BMSCs predifferentiated into cartilage prior to implantation. This strategy has failed to achieve formation of stable, hyaline-like cartilage, resistant to hypertrophy in vivo. We hypothesized that in vitro predifferentiation of BMSCs is not necessary when cells are combined with an adequate scaffold that supports the formation of stable cartilage in vivo. In this study, naïve (undifferentiated) human BMSCs were attached to dehydrothermally crosslinked stable fibrin microbeads (FMBs) without and with othe...
Critical Reviews in Oncology/Hematology, 2017
Melanoma is a highly lethal cancer deriving from transformed dermal melanocytes. Early diagnosed ... more Melanoma is a highly lethal cancer deriving from transformed dermal melanocytes. Early diagnosed primary melanoma may be curable, but the cure-rate of more advanced stages is limited, with high mortality rate. With the progression of the tumor, the melanocytes overexpress intracellular or cell-surface molecules, including ectopic normal and tumor-specific proteins. Some of these induce a specific immune response by T and B lymphocytes. Antibodies raised against melanoma antigens were proposed for differential disease diagnosis, staging, prognosis and evaluation of treatment efficiency. Nevertheless, treatments based on stimulation of specific antimelanoma immune responses have had only limited success. It seems that efficient immunotherapy should become more feasible pending on finding new adequate antigens to target. New insights into immune regulation of the tumor microenvironment and its progression may help the development of more successful treatments. We present here up-to-date information on known major melanoma-associated antigens, which could serve as tools for diagnosis as well as for clinical immunotherapy. This approach with promising results for treating some other selected malignancies is still experimental with a very limited success in melanoma. The development of new immune modulators of the tumor microenvironment and neo-antigens may be additional promising directions and may open new opportunities for the immunotherapy of melanoma.
Journal of Vascular Research, 2010
Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/jvr_issues 108 Antioxidants Reverse Age-Related Collateral Growth Impairment
International Journal of Dermatology, 1986
The concentrations of zinc (Zn), copper (Cu), and iron (Fe) in the skin have been noninvasively d... more The concentrations of zinc (Zn), copper (Cu), and iron (Fe) in the skin have been noninvasively determined in vivo by diagnostic x-ray spectrometry. The skin of healthy controls was divided into two major groups based upon the distribution of the concentrations of these elements. In the face and upper neck, the following wet weight concentrations were recorded: Fe, 14.2 +/- 3.3 ppm; Cu, 1.3 +/- 0.3 ppm; and Zn, 6.7 +/- 1.1 ppm. In the chest, abdomen, arm, axilla, and lower neck, the concentrations of these elements were as follows: Fe, 10.2 +/- 2.5 ppm; Cu, 0.8 +/- 0.3 ppm; and Zn, 4.5 +/- 1.7 ppm. In most lesions of solar dermatitis, solar keratosis, basal and squamous cell carcinomas, variable elevations of Zn and Fe (up to significant levels) were recorded in most of the contralateral, apparently uninvolved skin. In the majority of pigmented nevi and malignant melanomas, the levels of Fe and Zn were elevated. In some of these, the Cu concentration also was increased.
Zeitschrift für Parasitenkunde
ABSTRACT
Journal of Neuroimmunology, 2014
Cancer immunology, immunotherapy : CII, Jan 2, 2015
Targeted cancer immunotherapy is challenging due to the cellular diversity and imposed immune tol... more Targeted cancer immunotherapy is challenging due to the cellular diversity and imposed immune tolerance in the tumor microenvironment (TME). A promising route to overcome those drawbacks may be by activating innate immune cells (IIC) in the TME, toward tumor destruction. Studies have shown the ability to "re-educate" pro-tumor-activated IIC toward antitumor responses. The current research aims to stimulate such activation using a combination of innate activators loaded onto microparticles (MP). Four inducers of Toll-like receptors 4 and 7, complement C5a receptor (C5aR) and gamma Fc receptor and their combinations were loaded on MP, and their influence on immune cell activation evaluated. MP stimulation of immune cell activation was tested in vitro and in vivo using a subcutaneous B16-F10 melanoma model induced in C57BL6 mice. Exposure to the TLR4 ligand lipopolysaccharide (LPS) bound to MP-induced acute inflammatory cytokine and chemokine activity in vitro and in vivo, wi...
... 3,4 Moreover, the microenvironment substantially contributes to tumor escape by:5 limiting th... more ... 3,4 Moreover, the microenvironment substantially contributes to tumor escape by:5 limiting the action of the immune system; counteracting the performance of chemotherapeutic agents; Stem Cell-Based Tissue Repair Edited by Raphael Gorodetsky and Richard Schafer r The ...
Vaccine, 2007
Transcutaneous immunization aims at taking advantage of the skin's immune system for the purpose ... more Transcutaneous immunization aims at taking advantage of the skin's immune system for the purpose of immunoprotection. In the present study we evaluated the potential of topical delivery of a recombinant melanoma protein, HR-gp100, derived from a shorter sequence of the native gp100 gene. The protein was applied on the skin, with and without the addition of two forms of heat labile enterotoxin (nLT and LTB). HR-gp100 fused to Haptide, a cell penetrating 20mer peptide (HR-gp100H) was also tested. Topical HR-gp100 and HR-gp100H application on the ears of mice elicited the production of specific antibodies, and transcutaneous delivery to intact human skin induced dosedependent LC activation. nLT and LTB also activated LC, but did not further increase the activation induced by HR-gp100. These results show that HR-gp100, an antigenic tumor-derived protein, activates the immune system following transcutaneous delivery, as shown by both Langerhans cell activation and induction of antibody production.
Radiation Research, 1991
ABSTRACT
Nous avons developpe de nouvelles microbilles en fibrine (MBF) biodegradables, de 50 a 300 mm de ... more Nous avons developpe de nouvelles microbilles en fibrine (MBF) biodegradables, de 50 a 300 mm de diametre, pour servir de puissants vecteurs cellulaires. Les MBF se sont revelees haptotactiques vis-a-vis d'un vaste eventail de types cellulaires. Il s'agit notamment de cellules normales telles que les cellules primaires endotheliales, les cellules musculaires lisses, les fibroblastes, les chondrocytes et les osteoblastes, les progeniteurs osteogeniques de la moelle osseuse, ainsi que plusieurs cellules transformees, telles que les 3T3 et les lignees cellulaires de carcinome mammaire de souris. Les MBF ont fixe de maniere minimale les keratinocytes et differentes lignees cellulaires de la serie leucocytaire. Les cellules ont pu etre maintenues sur les MBF a des densites extremement elevees pendant plus de 2 semaines et elles ont pu etre transferees dans des tubes a ensemencer ou dechargees sans trypsination prealable. La microscopie optique, a fluorescence et laser confocale a...