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A phase III clinical results of INVOSSA™(TissueGene C): A clues for the potential disease modifying OA drug
S90
Poster Abstracts
thalassemia. However, the knock-out method with HbF production was more effective in this experiment. This is probably due to the design of the gRNA. Further experimentation is needed for effective correction using the knock-in method.
212 A PHASE III CLINICAL RESULTS OF INVOSSA™(TISSUEGENE C): A CLUES FOR THE POTENTIAL DISEASE MODIFYING OA DRUG J. Cho, T. Kim, J. Shin, S. Kang, B. Lee Kolon Life Science, Gwacheon, Republic of Korea Invossa™ (TissueGene C) is a cell and gene therapy for osteoarthritis that contains non-transformed and transduced chondrocytes by the ratio of 3:1. The transduced cell employs ex-vivo gene delivery via a retrovirally transduced chondrocytes that overexpress transforming growth factor β1 (TGF β1). The randomized double blind, multi-center, placebo-controlled phase III trials were conducted to determine both safety and efficacy in patients with knee osteoarthritis. Participants (n = 156) with a confirmed diagnosis of knee osteoarthritis by X-ray and MRI were randomized into the treatment group (Invossa™, n = 78) and the control group (saline, n = 78). The primary evaluation parameters were comparison of changes after 52 weeks from the baseline of International Knee Document Committee (IKDC) and VAS. The secondary parameters were evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS), Joint Space Width (JSW) with X-ray, Whole Organ Magnetic Resonance Imaging Score (WORMS) with MRI, and biomarkers from serum and urine samples. The observation period was one year after a single injection. The primary parameters, IKDC total score and in VAS score at 52 weeks were statistically significant (IKDC: P < 0.001; VAS: P < 0.001). The secondary parameters, WOMAC and KOOS, also showed statistically significant improvement in 1 year follow up after a single injection of Invossa™. With the quantitative MRI analysis, the Invossa™ treatment group showed improvement for the bone area and cartilage thickness. In summary, Phase III study indicated that Invossa™ treatment improved pain, sports activities, and quality of daily life in patients with knee osteoar-
thritis when compared to the placebo control. The Invossa™ treatment also showed clues of potential disease modifying OA drug.
213 EFFECT OF DIFFERENT CULTURE CONDITIONS ON NESTIN EXPRESSION IN FETAL PANCREAS DERIVED MESENCHYMAL STEM CELLS H. Aghayan2,1, k Falahzadeh2, B. Arjmand2, B. Larijani2 1 Regenerative Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran, 2Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran Introduction: Many studies have reported isolation of nestin positive cells from human pancreas.These studies have suggested nestin as a marker of islet progenitor cells and emphasized their role in beta cell regeneration. Studies on human fetal and adult pancreas have demonstrated that pancreas derived nestin positive cells show similar properties to mesenchymal stem cells. We previously reported a simple and growth factor-free protocol for generation of fetal pancreas mesenchymal stem cells (FPMSCs). Then, we tried to develop a xenofree protocol for clinical grade FPMSCs manufacturing. The objective of present study is to assess the effect of our xeno-free protocol on nestin expression in FPMSCs. Methods: Previously banked FPMSCs (third passage) were thawed and expanded in DMEM+10% FBS (group 1), DMEM+10% Human serum (group 2) or Xeno-free/Serum free media (group 3). After three consecutive passages, nestin expression was investigated by immunocytochemistry (ICC) and polymerase chain reaction (PCR). For ICC, FPMSCs were fixed, permeabilized, blocked and incubated in primary antibodies (Mouse anti human nestin, Vimentin, and Ki67) or isotype controls. Dako REAL EnVision kit was used for DAB staining. Total RNA was extracted from freshly isolated FPMSCs using RNeasy Mini Kit. cDNAs were synthesized and PCR were performed to identify the human Nestin gene expression.
Figure 1. Vimentin expression in different culture media.
Poster Abstracts
thalassemia. However, the knock-out method with HbF production was more effective in this experiment. This is probably due to the design of the gRNA. Further experimentation is needed for effective correction using the knock-in method.
212 A PHASE III CLINICAL RESULTS OF INVOSSA™(TISSUEGENE C): A CLUES FOR THE POTENTIAL DISEASE MODIFYING OA DRUG J. Cho, T. Kim, J. Shin, S. Kang, B. Lee Kolon Life Science, Gwacheon, Republic of Korea Invossa™ (TissueGene C) is a cell and gene therapy for osteoarthritis that contains non-transformed and transduced chondrocytes by the ratio of 3:1. The transduced cell employs ex-vivo gene delivery via a retrovirally transduced chondrocytes that overexpress transforming growth factor β1 (TGF β1). The randomized double blind, multi-center, placebo-controlled phase III trials were conducted to determine both safety and efficacy in patients with knee osteoarthritis. Participants (n = 156) with a confirmed diagnosis of knee osteoarthritis by X-ray and MRI were randomized into the treatment group (Invossa™, n = 78) and the control group (saline, n = 78). The primary evaluation parameters were comparison of changes after 52 weeks from the baseline of International Knee Document Committee (IKDC) and VAS. The secondary parameters were evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score (KOOS), Joint Space Width (JSW) with X-ray, Whole Organ Magnetic Resonance Imaging Score (WORMS) with MRI, and biomarkers from serum and urine samples. The observation period was one year after a single injection. The primary parameters, IKDC total score and in VAS score at 52 weeks were statistically significant (IKDC: P < 0.001; VAS: P < 0.001). The secondary parameters, WOMAC and KOOS, also showed statistically significant improvement in 1 year follow up after a single injection of Invossa™. With the quantitative MRI analysis, the Invossa™ treatment group showed improvement for the bone area and cartilage thickness. In summary, Phase III study indicated that Invossa™ treatment improved pain, sports activities, and quality of daily life in patients with knee osteoar-
thritis when compared to the placebo control. The Invossa™ treatment also showed clues of potential disease modifying OA drug.
213 EFFECT OF DIFFERENT CULTURE CONDITIONS ON NESTIN EXPRESSION IN FETAL PANCREAS DERIVED MESENCHYMAL STEM CELLS H. Aghayan2,1, k Falahzadeh2, B. Arjmand2, B. Larijani2 1 Regenerative Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran, 2Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran Introduction: Many studies have reported isolation of nestin positive cells from human pancreas.These studies have suggested nestin as a marker of islet progenitor cells and emphasized their role in beta cell regeneration. Studies on human fetal and adult pancreas have demonstrated that pancreas derived nestin positive cells show similar properties to mesenchymal stem cells. We previously reported a simple and growth factor-free protocol for generation of fetal pancreas mesenchymal stem cells (FPMSCs). Then, we tried to develop a xenofree protocol for clinical grade FPMSCs manufacturing. The objective of present study is to assess the effect of our xeno-free protocol on nestin expression in FPMSCs. Methods: Previously banked FPMSCs (third passage) were thawed and expanded in DMEM+10% FBS (group 1), DMEM+10% Human serum (group 2) or Xeno-free/Serum free media (group 3). After three consecutive passages, nestin expression was investigated by immunocytochemistry (ICC) and polymerase chain reaction (PCR). For ICC, FPMSCs were fixed, permeabilized, blocked and incubated in primary antibodies (Mouse anti human nestin, Vimentin, and Ki67) or isotype controls. Dako REAL EnVision kit was used for DAB staining. Total RNA was extracted from freshly isolated FPMSCs using RNeasy Mini Kit. cDNAs were synthesized and PCR were performed to identify the human Nestin gene expression.
Figure 1. Vimentin expression in different culture media.