{"title":"Mesenchymal stem cells-seeded bio-ceramic construct for bone regeneration in large critical-size bone defect in rabbit.","authors":"Swapan Kumar Maiti, Ajantha Ravindran Ninu, Palakkara Sangeetha, Dayamon D Mathew, Paramasivam Tamilmahan, Deepika Kritaniya, Naveen Kumar, Jurgen Hescheler","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Bone marrow derived mesenchymal stem cells (BMSC) represent an attractive cell population for tissue engineering purpose. The objective of this study was to determine whether the addition of recombinant human bone morphogenetic protein (rhBMP-2) and insulin-like growth factor (IGF-1) to a silica-coated calcium hydroxyapatite (HASi) - rabbit bone marrow derived mesenchymal stem cell (rBMSC) construct promoted bone healing in a large segmental bone defect beyond standard critical -size radial defects (15mm) in rabbits. An extensively large 30mm long radial ostectomy was performed unilaterally in thirty rabbits divided equally in five groups. Defects were filled with a HASi scaffold only (group B); HASi scaffold seeded with rBMSC (group C); HASi scaffold seeded with rBMSC along with rhBMP-2 and IGF-1 in groups D and E respectively. The same number of rBMSC (five million cells) and concentration of growth factors rhBMP-2 (50µg) and IGF-1 (50µg) was again injected at the site of bone defect after 15 days of surgery in their respective groups. An empty defect served as the control group (group A). Radiographically, bone healing was evaluated at 7, 15, 30, 45, 60 and 90 days post implantation. Histological qualitative analysis with microCT (µ-CT), haematoxylin and eosin (H & E) and Masson's trichrome staining were performed 90 days after implantation. All rhBMP-2-added constructs induced the formation of well-differentiated mineralized woven bone surrounding the HASi scaffolds and bridging bone/implant interfaces as early as eight weeks after surgery. Bone regeneration appeared to develop earlier with the rhBMP-2 constructs than with the IGF-1 added construct. Constructs without any rhBMP-2 or IGF-1 showed osteoconductive properties limited to the bone junctions without bone ingrowths within the implantation site. In conclusion, the addition of rhBMP-2 to a HASi scaffold could promote bone generation in a large critical-size-defect.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"12 2","pages":"87-99"},"PeriodicalIF":2.7,"publicationDate":"2016-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89718787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fatma M Elhusseini, Mohamed-Ahdy A A Saad, Nahla Anber, Doaa Elghannam, Mohamed-Ahmed Sobh, Aziza Alsayed, Sara El-Dusoky, Hussein Sheashaa, Hassan Abdel-Ghaffar, Mohamed Sobh
{"title":"Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats.","authors":"Fatma M Elhusseini, Mohamed-Ahdy A A Saad, Nahla Anber, Doaa Elghannam, Mohamed-Ahmed Sobh, Aziza Alsayed, Sara El-Dusoky, Hussein Sheashaa, Hassan Abdel-Ghaffar, Mohamed Sobh","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background/aims: </strong>Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system of both acute and chronic renal changes.</p><p><strong>Methods: </strong>This study used eighty Sprague-Dawley (SD) rats weighing 250-300g. They were assigned into four equal groups (each group n=20): (I) Negative control group, rats injected with single dose of 1 ml normal saline. (II) Positive control cisplatin, rats injected with a single dose of 5 mg/kg I.P in 1 ml saline. (III) Cisplatin and culture media group, rats injected with 0.5 ml of culture media single dose into the tail vein and (IV) Cisplatin and ADMSCs group, rats injected with a single dose of 0.5 ml of culture media containing 5 x10(6)ADMSCs into the tail vein one day after cisplatin administration. Each main group was further divided according to the timing of sacrifice into four subgroups (each subgroup n=5). Rats in the subgroup A were sacrificed after 4 days; subgroup B were sacrificed after 7 days; subgroup C were sacrificed after 11 days; and subgroup D were sacrificed after 30 days. Before sacrifice, 24 hrs.-urine was collected using a metabolic cage. Renal function was evaluated through blood urea nitrogen (BUN), serum creatinine and creatinine clearance. Kidney tissue homogenate oxidative stress parameters, Malondialdehyde (MDA), Superoxide dismutase (SOD) and Glutathione (GSH) were determined. In addition, histopathological analysis for active injury, regenerative and chronic changes was performed.</p><p><strong>Results: </strong>ADMSCs were characterized and their capability of differentiation was proved. Cisplatin induced a significant increase in plasma creatinine and tissue MDA and induced a decrease in SOD, GSH and creatinine clearance. ADMSCs attenuated these changes. Cisplatin resulted in prominent histopathological changes in the term of tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. ADMSCs significantly lowered the injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4 and limited fibrotic score at day 30.</p><p><strong>Conclusion: </strong>ADMSCs have both protective and regenerative abilities with consequent limitation of the development of renal fibrosis after the cisplatin induced acute tubular necrosis, largely through an anti-oxidative activity.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"12 1","pages":"36-48"},"PeriodicalIF":2.7,"publicationDate":"2016-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34544308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stem Cells Therapy in Multiple Sclerosis - A New Hope for Progressive Forms.","authors":"Samar S Ayache, Moussa A Chalah","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and represents a major cause of disability in young adults. Nowadays, the dichotomy between demyelination and neurodegeneration has been challenged, and both processes are believed to occur independently early in the disease process. 'Relapsing-remitting' MS is the most common subtype which generally shifts to a 'secondary progressive' form; MS progression is usually accompanied by a worsening of the motor, cognitive and emotional symptoms, as well as an increase in the disability level. Primary progressive MS represents a third subtype with severe disability scores, poor prognosis, and usually symptomatic management. In this perspective, an ideal therapy should have immunomodulatory, neuroprotective, regenerative and remyelinating potentials. Here, we discuss the promising abilities of stem cells therapies in patients with MS. The available data are tackled aiming to overcome the previously faced limitations and pave the way for larger scale randomized and controlled studies. </p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"12 1","pages":"49-51"},"PeriodicalIF":2.7,"publicationDate":"2016-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34544309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takumi Takeuchi, Akiko Tonooka, Yumiko Okuno, Mami Hattori-Kato, Koji Mikami
{"title":"Oct4B, CD90, and CD73 are upregulated in bladder tissue following electro-resection of the bladder.","authors":"Takumi Takeuchi, Akiko Tonooka, Yumiko Okuno, Mami Hattori-Kato, Koji Mikami","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Aim: </strong>We tested the hypothesis that stimulation by electro-resection of bladder tissue induces stem cells in the tissue repair process.</p><p><strong>Materials & methods: </strong>After primary transurethral resection of a bladder tumor and surrounding tissue (TUR-Bt), second TUR-Bt was performed. Tissues excised by second TUR-Bt were immunohistochemically stained for Oct4, a marker of pluripotency, and for CD90 and CD73, markers of mesenchymal stromal cells, when no bladder tumor cells remained.</p><p><strong>Results and conclusions: </strong>Oct4B protein was sporadically stained in the cytoplasm of interstitial cells in four out of eight cases. CD90 and CD73 are upregulated in interstitial and vascular endothelial cells without CD45 expression. Mesenchymal stromal cells, but not pluripotent stem cells, may be mainly involved in bladder tissue repair.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"12 1","pages":"10-5"},"PeriodicalIF":2.7,"publicationDate":"2016-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34544305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effect of Pro-Neurogenic Gene Expression on Adult Subventricular Zone Precursor Cell Recruitment and Fate Determination After Excitotoxic Brain Injury.","authors":"Kathryn S Jones, Bronwen J Connor","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Despite the presence of on-going neurogenesis in the adult mammalian brain, neurons are generally not replaced after injury. Using a rodent model of excitotoxic cell loss and retroviral (RV) lineage tracing, we previously demonstrated transient recruitment of precursor cells from the subventricular zone (SVZ) into the lesioned striatum. In the current study we determined that these cells included migratory neuroblasts and oligodendrocyte precursor cells (OPC), with the predominant response from glial cells. We attempted to override this glial response by ectopic expression of the pro-neurogenic genes Pax6 or Dlx2 in the adult rat SVZ following quinolinic acid lesioning. RV-Dlx2 over-expression stimulated repair at a previously non-neurogenic time point by enhancing neuroblast recruitment and the percentage of cells that retained a neuronal fate within the lesioned area, compared to RV-GFP controls. RV-Pax6 expression was unsuccessful at inhibiting glial fate and intriguingly, increased OPC cell numbers with no change in neuronal recruitment. These findings suggest that gene choice is important when attempting to augment endogenous repair as the lesioned environment can overcome pro-neurogenic gene expression. Dlx2 over-expression however was able to partially overcome an anti-neuronal environment and therefore is a promising candidate for further study of striatal regeneration. </p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"12 1","pages":"25-35"},"PeriodicalIF":2.7,"publicationDate":"2016-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34544307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cues for Cure; From within.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"12 1","pages":"1"},"PeriodicalIF":2.7,"publicationDate":"2016-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34655143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epigallocatechin Gallate Inhibits Mouse Mesenchymal Stem Cell Differentiation to Adipogenic Lineage.","authors":"Baldeep Chani, Veena Puri, Ranbir Chander Sobti, Sanjeev Puri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epigallocatechin gallate (EGCG) is a major component of green tea polyphenols having a potent anti-oxidant potential. Besides inhibiting the growth of many cancer cell types and inducing proliferation and differentiation in keratinocytes, it has been shown to promote reduction of body fat. The fact that mesenchymal stem cells (MSCs) have ability to self-renew and differentiate into the cells of mesodermal lineages, such as fat and bone, it is, thus, possible that EGCG may directly be involved in affecting fat metabolism through its effect on mesenchymal stem cells. Hence, with this aim, the present study was designed to determine the effect of EGCG on mouse mesenchymal stem cells, C3H10T1/2 cells differentiation into adipocytes. To understand this process, the cells were incubated with varying concentrations of EGCG (1 μM, 5 μM, 10 μM, 50 μM) in the presence and /or absence of adipogenic medium for 9 days. The results demonstrated that, EGCG inhibited the cells proliferation, migration and also prevented their differentiation to adipogenic lineage. These effects were analyzed through the inhibition of wound healing activity, reduction in Oil red O stained cells, together with decrease in the expression of Adipisin gene following EGCG treatment. These observations thus demonstrated anti-adipogenic effect of EGCG with a possibility of its role in the therapeutic intervention of obesity. </p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"12 1","pages":"16-24"},"PeriodicalIF":2.7,"publicationDate":"2016-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34544306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephany Cares Huber, José Luiz Rosenberis Cunha Júnior, Silmara Montalvão, Letícia Queiroz da Silva, Aline Urban Paffaro, Francesca Aparecida Ramos da Silva, Bruno Lima Rodrigues, José Fabio Santos Duarte Lana, Joyce Maria Annichino-Bizzacchi
{"title":"In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release.","authors":"Stephany Cares Huber, José Luiz Rosenberis Cunha Júnior, Silmara Montalvão, Letícia Queiroz da Silva, Aline Urban Paffaro, Francesca Aparecida Ramos da Silva, Bruno Lima Rodrigues, José Fabio Santos Duarte Lana, Joyce Maria Annichino-Bizzacchi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated.</p><p><strong>Methods: </strong>Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis.</p><p><strong>Results: </strong>A similar concentration of thrombin was observed in serum, L-PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release.</p><p><strong>Conclusions: </strong>The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension.</p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"12 1","pages":"2-9"},"PeriodicalIF":2.7,"publicationDate":"2016-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34655144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fangjing Wang, Saada Eid, James E Dennis, Kenneth R Cooke, Jeffery J Auletta, Zhenghong Lee
{"title":"Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation.","authors":"Fangjing Wang, Saada Eid, James E Dennis, Kenneth R Cooke, Jeffery J Auletta, Zhenghong Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) have shown promise as treatment for graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (alloBMT). Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs) were injected via carotid artery (IA) or tail vein (TV) into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI) using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [(99m)Tc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole-body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments. </p>","PeriodicalId":17155,"journal":{"name":"Journal of Stem Cells & Regenerative Medicine","volume":"11 2","pages":"34-43"},"PeriodicalIF":2.7,"publicationDate":"2015-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34489741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}