Roles of Mesenchymal Stem Cells (MSCs) in bacterial diseases

Palaksha K Javaregowda, Yoon Jang Won, Jang Goo 충북대학교 동물의학연구소 2013 Journal of Biomedical and Translational Research Vol.14 No.4

Mesenchymal stem cell (MSC) based cell therapy has emerged as a promising therapeutic approach for treatment of several degenerative, infectious and non-infectious diseases. Numerous studies have demonstrated the remarkable immunosuppressive and antibacterial effects of MSCs both in vitro and in vivo, in animal models and in humans. However, the antibacterial effects of MSCs rely heavily on their paracrine factors rather than direct cell-to-cell contact and the effect is specific to disease and site of infection or injury. Furthermore, recent studies have demonstrated the double-edged sword effect of MSCs in bacterial infectious diseases. Despite their inherent potential for repair of damaged tissues, immunosuppression, and alleviation of various autoimmune as well as infectious diseases, MSCs also play a critical role in promoting persistent bacterial infection and disease progression. Therapeutic administration of MSCs successfully inhibited the bacterial growth and enhances survival by improved clearance of pathogenic bacteria in sepsis and pneumonic conditions. However, due to their abnormal transformation, they assist in long lasting survival and persistent infection of Mycobacterium tuberculosis (M. tuberculosis) and may also be responsible for progression of gastric cancer. This review focuses on recent advances that have broadened our understanding of MSC based therapy for bacterial diseases and provides new insight into the possible therapeutic targets of fatal bacterial diseases.

Roles of Mesenchymal Stem Cells (MSCs) in bacterial diseases

Palaksha K Javaregowda,윤장원,장구 충북대학교 동물의학연구소 2013 Journal of Biomedical and Translational Research Vol.14 No.4

Mesenchymal stem cell (MSC) based cell therapy has emerged as a promising therapeutic approach for treatment of several degenerative, infectious and non-infectious diseases. Numerous studies have demonstrated the remarkable immunosuppressive and antibacterial effects of MSCs both in vitro and in vivo, in animal models and in humans. However, the antibacterial effects of MSCs rely heavily on their paracrine factors rather than direct cell-to-cell contact and the effect is specific to disease and site of infection or injury. Furthermore, recent studies have demonstrated the double-edged sword effect of MSCs in bacterial infectious diseases. Despite their inherent potential for repair of damaged tissues, immunosuppression, and alleviation of various autoimmune as well as infectious diseases, MSCs also play a critical role in promoting persistent bacterial infection and disease progression. Therapeutic administration of MSCs successfully inhibited the bacterial growth and enhances survival by improved clearance of pathogenic bacteria in sepsis and pneumonic conditions. However, due to their abnormal transformation, they assist in long lasting survival and persistent infection of Mycobacterium tuberculosis (M. tuberculosis) and may also be responsible for progression of gastric cancer. This review focuses on recent advances that have broadened our understanding of MSC based therapy for bacterial diseases and provides new insight into the possible therapeutic targets of fatal bacterial diseases.

Morphological Changes of Bones and Joints with Rheumatoid Arthritis and Osteoarthritis

Hong, Yun-Kyung,Javaregowda, Palaksha Kanive,Lee, Sang-Kil,Lee, Sang-Rae,Chang, Kyu-Tae,Hong, Yong-Geun The Korean Society of Animal Reproduction 2011 Reproductive & developmental biology Vol.35 No.2

Arthritis is a common disease in aged people, and is clinically divided into rheumatoid arthritis (RA) and osteoarthritis (OA). Although common symptoms such as pain are present, the underlying pathological mechanisms are slightly different. Therefore, the objectives of the present study were to compare joint damage induced by RA and OA by analyzing the major morphological and molecular differences, and to propose a suitable therapeutic intervention based on the pathophysiological conditions of bones and joints. For the RA animal model, 8-week-old DBA1/J mice were immunized with bovine type II collagen emulsified in complete Freund's adjuvant (CFA). Normal C57BL/6 mice (over 2 years of age) were used for OA. The clinical arthritis score was calculated using a subjective scoring system, and paw thicknesses were measured using calipers. The serum TNF ${\alpha}$ level was analyzed using an ELISA kit. Micro-CT was used to identify pathological characteristics and morphological changes. In collagen-induced RA mice, there were increased ankle joint volumes and clinical scores (p<0.01). The concentration of TNF ${\alpha}$ was significantly increased from 3 to 7 weeks after immunization. Micro-CT images showed trabecular bone destruction, pannus formation, and subchondral region destruction in RA mice. OA among aged mice showed narrowed joint spaces and breakdown of articular cartilage. This study suggests that a careful therapeutic intervention between RA and OA is required, and it should be based on morphological alteration of bone and joint.

Morphological Changes of Bones and Joints with Rheumatoid Arthritis and Osteoarthritis

Yunkyung Hong,Palaksha Kanive Javaregowda,Sang-Kil Lee,Sang-Rae Lee,Kyu-Tae Chang,Yonggeun Hong 한국동물번식학회 2011 Reproductive & developmental biology Vol.35 No.2

Rheumatic Arthritis-induced Alteration of Morphology and Function in Muscles

Yunkyung Hong,Joo-Heon Kim,Palaksha Kanive Javaregowda,Sang-Kil Lee,Sang-Rae Lee,Kyu-Tae Chang,Yonggeun Hong 한국동물번식학회 2011 Reproductive & developmental biology Vol.35 No.2

Rheumatic Arthritis-induced Alteration of Morphology and Function in Muscles

Hong, Yun-Kyung,Kim, Joo-Heon,Javaregowda, Palaksha Kanive,Lee, Sang-Kil,Lee, Sang-Rae,Chang, Kyu-Tae,Hong, Yong-Geun The Korean Society of Animal Reproduction 2011 Reproductive & developmental biology Vol.35 No.2

Clinical arthritis is typically divided into rheumatoid arthritis (RA) and osteoarthritis (OA). Arthritis-induced muscle weakness is a major problem in aged people, leading to a disturbance of balance during the gait cycle and frequent falls. The purposes of the present study were to confirm fiber type-dependent expression of muscle atrophy markers induced by arthritis and to identify the relationship between clinical signs and expression of muscle atrophy markers. Mice were divided into four experimental groups as follows: (1) negative control (normal), (2) positive control (CFA+acetic acid), (3) RA group (CFA+acetic acid+type II collagen), and (4) aging-induced OA group. DBQA/1J mice (8 weeks of age) were injected with collagen (50 ${\mu}g/kg$), and physiological (body weight) and pathological (arthritis score and paw thickness) parameters were measured once per week. The gastrocnemius muscle from animals in each group was removed, and the expression of muscle atrophy markers (MAFbx and MuRF1) and myosin heavy chain isoforms were analyzed by reverse transcription-polymerase chain reaction. No significant change in body weight occurred between control groups and collagen-induced RA mice at week 10. However, bovine type II collagen induced a dramatic increase in clinical score or paw thickness at week 10 (p<0.01). Concomitantly, the expression of the muscle atrophy marker MAFbx was upregulated in the RA and OA groups (p<0.01). A dramatic reduction in myosin heavy chain (MHC)-$I{\beta}$ was seen in the gastrocnemius muscles from RA and OA mice, while only a slight decrease in MHC-IIb was seen. These results suggest that muscle atrophy gene expression occurred in a fiber type-specific manner in both RA- and OA-induced mice. The present study suggests evidence regarding why different therapeutic interventions are required between RA and OA.

Seasonal variation and comparative analysis of non-specific humoral immune substances in the skin mucus of olive flounder (Paralichthys olivaceus)

Jung, T.S.,del Castillo, C.S.,Javaregowda, P.K.,Dalvi, R.S.,Nho, S.W.,Park, S.B.,Jang, H.B.,Cha, I.S.,Sung, H.W.,Hikima, J.i.,Aoki, T. Pergamon Press ; Elsevier Science Ltd ; Pergamon 2012 DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY Vol.38 No.2

The epidermal secretion of fish contains various non-specific immune substances that act as the first line of defense against invading pathogens. The present study investigated the level of mucosal antibodies, the activities of hemagglutinin and protease, and other enzymes in the skin mucus of farm reared olive flounder (Paralichthys olivaceus) for 1year, in order to gain an insight into the relationship between these mucosal immune substances and their seasonal variation. These levels varied significantly during different months of sample collection. The present study showed a positive correlation between water temperature and the level of mucosal antibodies, and an inverse relationship between the level of mucosal antibodies and the activity of mucosal hemagglutinin and protease, but no relationship between lysozyme activity and other innate immune substances. This relationship is thought to be a compensatory response in olive flounder to protect itself against pathogenic microorganisms which are inherently present in the aquatic environment.

Role of Cel5H protein surface amino acids in binding with clay minerals and measurements of its forces

Math Renukaradhya K.,Nagakumar Bharatham,Palaksha K. Javaregowda,윤한대 한국현미경학회 2021 Applied microscopy Vol.51 No.1

Our previous study on the binding activity between Cel5H and clay minerals showed highest binding efficiency among other cellulase enzymes cloned. Here, based on previous studies, we hypothesized that the positive amino acids on the surface of Cel5H protein may play an important role in binding to clay surfaces. To examine this, protein sequences of Bacillus licheniformis Cel5H ( Bl Cel5H) and Paenibacillus polymyxa Cel5A ( Pp Cel5A) were analyzed and then selected amino acids were mutated. These mutated proteins were investigated for binding activity and force measurement via atomic force microscopy (AFM). A total of seven amino acids which are only present in Bl Cel5H but not in Pp Cel5A were selected for mutational studies and the positive residues which are present in both were omitted. Of the seven selected surface lysine residues, only three mutants K196A(M2), K54A(M3) and K157T(M4) showed 12%, 7% and 8% less clay mineral binding ability, respectively compared with wild-type. The probable reason why other mutants did not show altered binding efficiency might be due to relative location of amino acids on the protein surface. Meanwhile, measurement of adhesion forces on mica sheets showed a well-defined maximum at 69 ± 19 pN for wild-type, 58 ± 19 pN for M2, 53 ± 19 pN for M3, and 49 ± 19 pN for M4 proteins. Hence, our results demonstrated that relative location of surface amino acids of Cel5H protein especially positive charged amino acids are important in the process of clay mineral-protein binding interaction through electrostatic exchange of charges.

Autologous Bone Marrow Mesenchymal Cell Induced Chondrogenesis for the Treatment of Osteoarthritis of Knee

허성우,Asode Ananthram Shetty,김장묵,조미라,김선애,양시영,김영주,Palaksha Kanive Javaregowda,최남용,강진,김석중 한국조직공학과 재생의학회 2016 조직공학과 재생의학 Vol.13 No.2

Healthy and high quality of life has become the main issue with increasing human life span. Many biological treatments for osteoarthritis of the knee have been tried with limited success. We compared data from 7 patients who underwent total knee arthroplasty and 46 patients who underwent autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) for osteoarthritis of grade IV of the Kellgren-Lawrence classification and grade IV of modified Outerbridge classification from 50 to 65 years of age. Clinical evaluation of the 2 groups showed significant improvement in the mean telephone Knee Society Scoring system (tKSS)-A (pain) and tKSS-B (function) scores throughout the postoperative follow-up period. There was no difference in the patients’ satisfaction between the 2 groups. MCIC is a treatment option at least for delaying disease progression of osteoarthritis of the knee.

Oct4 overexpression facilitates proliferation of porcine fibroblasts and development of cloned embryos

Kim, Su Jin,Koo, Ok Jae,Park, Hee Jung,Moon, Joon Ho,da Torre, Bego Roibas,Javaregowda, Palaksha Kanive,Kang, Jung Taek,Park, Sol Ji,Saadeldin, Islam M.,Choi, Ji Yei,Lee, Byeong-Chun,Jang, Goo Cambridge University Press 2015 Zygote Vol.23 No.5

<B>Summary</B><P>Octamer-binding transcription factor 4 (Oct4) is a critical molecule for the self-renewal and pluripotency of embryonic stem cells. Recent reports have shown that Oct4 also controls cell-cycle progression and enhances the proliferation of various types of cells. As the high proliferation of donor fibroblasts is critical to the production of transgenic pigs, using the somatic cell nuclear transfer technique, we analysed the effect of Oct4 overexpression on the proliferation of porcine fibroblasts and embryos. Porcine endogenous Oct4 cDNA was cloned, sequenced and inserted into an expression vector. The vector was transfected into porcine fibroblasts, and a stable Oct4-overexpressed cell line was established by antibiotic selection. Oct4 expression was validated by the immunostaining of Oct4. Cell morphology was changed to sharp, and both proliferation and migration abilities were enhanced in Oct4-overexpressed cells. Real-time RT-PCR results showed that <I>p16</I>, <I>Bcl2</I> and <I>Myc</I> were upregulated in Oct4-overexpressed cells. Somatic cell nuclear transfer was performed using Oct4-overexpressed cells, and the development of Oct4 embryos was compared with that of wild-type cloned embryos. The cleavage and blastocyst formation rates were improved in the Oct4 embryos. Interestingly, blastocyst formation of the Oct4 embryos was observed as early as day 5 in culture, while blastocysts were observed from day 6 in wild-type cloned embryos. In conclusion, the overexpression of Oct4 enhanced the proliferation of both porcine fibroblasts and embryos.</P>