Umbilical cord derived mesenchymal stem cell therapy for osteoarthritis: a consolidated review

Osteoarthritis (OA) is a leading cause of degenerative disease and is the most common persistent condition worldwide. The common burden imposed by OA significantly damages the articular cartilage, which results in pain and seriously impacts the quality of life in the affected people. Disease progression is assumed to increase with obesity and aging. The current therapies include weight loss, activity adjustment, traditional pain management and replacement of the affected joint. To overcome these limitations, recently, cell-based therapies mainly Umbilical cord derived Mesenchymal stem cell (UC-MSC) have become an attractive cell source for an allogeneic mesenchymal stem cell to repair and regenerate the structure and function of articular tissues. Although the mechanism is not clearly defined, it is believed that the paracrine signaling, inflammatory response, and immunomodulatory role of UC-MSCs play a crucial role in developing a treatment approach of OA. The purpose of this review was to outline the advantages of using UC-MSCs in treating OA. This review also discusses the possible hurdles that stand in the way of successful implementation of UC-MSC as a routine treatment regimen for OA

Alternative and complementary therapies in osteoarthritis and cartilage repair

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of ‘alternative’ therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects

Millifluidic-assisted ionic gelation technique for encapsulation of probiotics in double-layered polysaccharide structure

A unique double-layered vehicle was fabricated for the first time based on a millifluidic/direct gelation to encapsulate probiotics. Free probiotic bacteria are usually very sensitive to severe gastrointestinal conditions and maintaining their survival when passing through the digestive tract is essential. The effects of alginate concentration (20–30 g/L), flow rates of alginate (0.8–1.2 mL/min), and W/O emulsion (0.5–0.7 mL/min) on encapsulation efficiency (EE), size, and sphericity of core–shell millicapsules were optimized for encapsulation of Bifidobacterium animalis subsp. lactis and Lactobacillus plantarum. The optimized calcium-alginate millicapsule was spherical (0.97 ± 0.01 SF), with an average diameter of 4.49 ± 0.19 mm, and encapsulation efficiency of 98.17 ± 0.5 %. Two strains were encapsulated separately in W/O emulsion as a core of the millicapsule. After coating with chitosan, the encapsulation yield of the bacteria, survival rates under simulated gastrointestinal (GI) conditions, and viability during storage were determined. Survival efficiency of B. animalis subsp. lactis and L. plantarum after millifluidic encapsulation were found to be 92.33 and 90.81 %, respectively. Cell viability of encapsulated probiotics after passing through the GI system was improved (7.5 log CFU mL−1 for both strains). Although the viability of the encapsulated probiotics stored at −18 °C for five months significantly decreased (p<0.05), the number of live cells was approximately in accordance with the standard definition of long-term probiotic survival (6 log CFU/g). This work provides a pathway for the construction of an innovative delivery system with high efficiency and protective effects for probiotics

The clinical efficacy of intraarticular administration of bone marrow aspirate concentrate, platelet rich plasma and hyaluronic acid in the treatment of the knee osteoarthritis

Osteoartritis kolena predstavlja progresivno degenerativno oboljenje svih struktura kolena koji je u porastu kako u svetu tako i u našoj zemlji i predstavlja veliko opterećenje za pacijenta i njegovu porodicu ali i za zdravstveni sistem zemlje. Pored ranije definisanih etioloških faktora poput genetske predispozicije, gojaznosti, posledice traume i poremećene osovine donjeg ekstremiteta, u poslednje vreme se kao uzroci povećanja incidence ove bolesti kod mladih navode i posledice netretiranih povreda hrskavice, meniskusa i ligamenata kolena kao i sportske i radne aktivnosti sa repetitivnim mikrotaumama kolena. Lečenje ove bolesti podrazumeva kako više načina konzervativnog lečenja lekovima, modifikacijama aktivnosti, fizikalnom terapijom i intraartikularnim injekcijama tako i različitim hirurškim procedurama. U najvećem broju slučajeva, bolest progredira do faze kada je neophodna ugradnja totalne proteze kolena sa svim svojim benefitima i komplikacijama i velikom cenom koštanja i opterećenja za zdravstveni sistem. Unazad oko jednu deceniju, u svetskoj i domaćoj literaturi se kao opcije lečenja osteoartritisa kolena navode i regenerativne ili ortobiološke procedure koje podrazumevaju ubrizgavanje ili implantaciju autologih tkiva, pre svega ćelijskih koncentrata ili određenih autologih proteina, koji imaju antiinflamatorno i analgetsko dejstvo i sposobnost pokretanja anaboličkih i regenerativnih procesa u zglobu kolena. METOD: Prospektivna klinička studija koja je rađena na Klinici za ortopedsku hirurgiju i traumatologiju Kliničkog centra Vojvodine i uključila je 176 pacijenata koji su raspoređeni u tri grupe i tretirani intraartikularnom injekcijom koncentrata aspirata koštane srži (Angel Arthrex BMAC set), plazmom obogaćenom trombocitima (LR-PRP Tr 7-8 x baseline, Le 2-3 x Baseline) i preparatima HA - hijaluronske kiseline (inj. Cartinorm 20ml/2mg po jedna injekcija na 7 dana 3 nedelje) i koji su potom praćeni preinterventno i nakon 3, 7, 14, 21 dan i 1, 3, 6, 9 i 12 meseci. Injekcije su davane u koleno kod BMAC grupe kroz tri injekciona portala: suprapatelarno lateralno, infrapatelarno lateralno i medijalno dok su kod druge dve grupe inekcije aplikovane kroz identičan, lateralni suprapatelarni portal. Praćenje je podrazumevalo fizikalni pregled i popunjavanje upitnika VAS skale preinterventno i u prvom mesecu kao i KOOS, IKDC, WOMAC i SF 36 skale preinterventno i nakon 1,3,6,9 i 12 meseci, te davanjem informacija o komforu same procedure, uzimanju lekova nakon procedure i odlasku na fizikalnu terapiju. Statistička obrada je vršena standardnim metodama ( Hi-kvadrat test, analiza varijanse) uz upotrebu SPSS 20.0 softvera. REZULTATI: Ispitivane grupe nisu se razlikovale u pogledu pola, starosti, indeksu telesne mase i težine artroze kolena. Bol je kod svih grupa statistički značajno opao već nakon tri dana i to stanje se održalo do 21 dan ali je izraženiji pad bola zabeležen kod BMAC grupe. Na merenjima od mesec dana do 12 meseci, došlo je do statistički značajnog poboljšanja u svim skalama sve do dvanaestog meseca sa tim što je poboljšanje bilo izraženije u grupi BMAC u odnosu na druge dve grupe sa statističkom značajnošću između BMAC i HA grupe ali bez značajnosti između BMAC i PRP grupe kao i izmeću PRP i HA grupe, iako su svi parametri bili bolji kod grupe PRP u odnosu na grupu HA. Nije bilo statistički značajne razlike u parametrima kliničkog poboljšanja kod pacijenata tretiranih sa BMAC u odnosu na izbor portala za davanje injekcije. Nije zabeležen ni jedan ozbiljan neželjeni događaj tokom praćenja od 12 meseci a da je povezan sa intervencijom na kolenu. ZAKLJUČAK: Sve tri intervencije postižu dobre kliničke rezultate u smislu smanjenja bola i povećanja fukcije obolelog kolena u odnosu na preinterventni period koji traju i preko godinu dana. BMAC je terapija koja je klinički efikasnija u odnosu na PRP i HA terapiju. Sve tri metode su bezbedne i efikasne bez obzira na mesto davanja injekcije u koleno.Osteoarthritis is a progressive degenerative disease which include changes in all joint structures. The incidence of this disease is rising both in the world and in our country and represents a great burden for the patients and for their families as well as for overall health and socioeconomic system of the country. In addition to the well-known etiological factors such as genetic predisposition, obesity, consequences of trauma and malalignment of the lower extremity, the consequences of untreated injuries of cartilage, meniscus and knee ligaments as well as sports and work activities with repetitive knee microtaumas have recently been reported. Treatment of this disease includes several conservative treatment options such as non-steroid anti-inflammatory drugs, modifications of activities, physiotherapy and intra-articular injections, as well as various surgical procedures. In most cases, the disease progresses to the stage when total joint replacement is inevitable with all its benefits and complications and the high cost and burden on the health system. About a decade ago, in the world and national literature, regenerative or ortho-biological procedures comprising the injection or implantation of autologous tissues, primarily cellular concentrates or certain autologous proteins, whith anti-inflammatory and analgesic effects and the ability to move, have been introduced as a treatment options for osteoarthritis of the knee. METHOD: A prospective clinical study was conducted at the Departement for Orthopedic Surgery and Traumatology of the Clinical Center of Vojvodina and included 176 patients. The patients were divided into three groups, each of them treated with single intra-articular injection of Bone Marrow Aspirate Concentrate (Angel Arthrex BMAC set), Platelet rich Plasma single injection (Tr 7-8 x baseline, Le 2-3 x Baseline) or HA-hyaluronic acid injections (inj. Cartinorm 20ml / 2mg one injection every 7 days for 3 weeks). The patients were observed before the intervention and followedup after 3,7,14, 21 days and 1, 3, 6, 9 and 12 months. In the BMAC group, the maedication was admistrated through the three most popular injection portals (suprapatellar lateral, infrapatellar lateral and medial) , while in the other two groups were injected through the lateral suprapatelar portal. Monitoring included physical examination and completion of the VAS scale questionnaire preintervention and durintg the first month as well as KOOS, IKDC, WOMAC and SF 36 scales preintervention and after 1,3,6,9 and 12 months. We also provided information about the comfort of the procedure, usage of medication after the procedure and potential performance of physiotherapy. Statistical calculations were performed by standard methods (Chi-Square test, ANOVA) with SPSS 20.0 software. RESULTS: The study groups did not differ in terms of gender, age, body weight, and severity of knee osteoarthritis. Pain in all groups decreased significantly after three days, and this condition remained for 21 days. Pain decrease observed in the BMAC group was noteworthy. Concerning measurements from one month to 12 months, there were significant improvements in all scales up to the twelfth month, with the improvement being more pronounced in the BMAC group compared to the other two groups.There was statistically significance between BMAC and HA group but without significance between BMAC and PRP groups as well as between PRP and HA groups, although all parameters were better in the PRP group, compared to the HA group. There were no statistically significant differences in the parameters of clinical improvement in patients treated with BMAC concerning the injection portal location. There were no serious adverse events during the 12-month follow-up that were associated with knee intervention. CONCLUSION: All three interventions achieved good clinical results in terms of reducing pain and increasing the function of the affected knee, compared to the pre-intervention period. Positive results, , that were achieved persisted over 12 months. BMAC showed some advantages comparing to PRP, and proved to be significantly more effective than HA therapy. All three methods are safe and effective regardless of the injection site in the knee

Storia dei gruppi di opposizione a Bourguiba e loro eredità nella Tunisia post-2011. Proposte per una cooperazione dal basso.

Nel 2011 la Tunisia sembra emergere da un "vuoto politico" dovuto a più di 50 anni di dittatura. Anche per colmare questo vuoto si sono riversati nel Paese ingenti somme per lo "sviluppo della democrazia". In questa tesi si vuole mostrare come in realtà in Tunisia vi fosse, fin dai tempi di Bourguiba, un complesso e articolato insieme di gruppi di opposizione politica che hanno avuto e hanno tuttora un ruolo nello sviluppo del Paese. Per una reale cooperazione con i cittadini tunisini in Tunisia, ma anche in Italia e in Europa, è quindi necessario conoscere tali movimenti e la loro storia

Il processo di costituzionalizzazione in Tunisia e i diritti dei vulnerabili: minoranze, donne e bambini

[ita] In questo lavoro di ricerca si è tentato di rispondere alla domanda se la teoria dell’universalità di certi diritti come quelli riguardanti i vulnerabili, in particolare le minoranze, donne e bambini, possa essere estesa anche a Paesi di fede musulmana che, al contrario, insistono sulla specificità culturale. È il caso della Tunisia che si è scelto di studiare in virtù del suo passato ricco di civilizzazioni e del nuovo processo di democratizzazione in corso, senza trascurare l’importanza della sua adesione a interessanti accordi internazionali come il Patto di Barcellona. Si è quindi compreso che l’ostacolo alla protezione di certi diritti non può essere attribuito solo alla religione poiché, anche se le diverse confessioni non esistessero, non sarebbe ugualmente facile garantire il rispetto incondizionato dei diritti dei vulnerabili, in particolare di quelle minoranze come gli handicappati e gli omosessuali, che non possono mai diventare, né diventeranno, una maggioranza. Al fine di ridurre e / o risolvere queste forti disparità relative a qualsivoglia ordinamento giuridico, compreso quello del Paese studiato, sarà necessario rendere la libertà di coscienza un principio generale ed efficace erga omnes e assicurare che la società civile sia rafforzata e sensibilizzata verso la tutela dei diritti fondamentali. Ciò dovrà avvenire non solo a livello locale ma universale, attraverso un dialogo tra maggioranze e minoranze, nel segno della vera democrazia, superando l'ostilità delle élites politiche che, il più delle volte, dietro le varie dichiarazioni di principio calpestano i diritti umani per scopi economici.[eng] The aim of this work is to answer the research question of whether the theory of universality of certain rights such as those concerning the vulnerable, in particular minorities, women and children, can also be extended to muslim countries, which still insist on cultural specificity instead. Consequently, we decided to study the case of Tunisia, because of both its past full of different civilizations, and the new ongoing process of democratization, and the importance of its subscription to interesting international agreements, such as the Barcelona Pact. What was understood within this thesis is that the obstacle to the protection of certain rights cannot be blamed only on religion; in fact, even if different religions did not exist, it would not be easy as well to guarantee the unconditional respect of the rights of the vulnerable, especially of those minorities such as handicapped and homosexsuals, that unfortunately cannot and will never become a majority. Therefore, in order to reduce and / or resolve these strong disparities related to any legal system, including that of the studied country, it will be necessary to make freedom of conscience a general and effective principle erga omnes, and to ensure that civil society is strengthened and sensitized towards the protection of fundamental rights. This will have to take place not only on a local but also on a universal level, by exploiting dialogue between majorities and minorities, according to the principles of a real democracy. In this way, it would be possible to finally overcome the hostility of political élites which, most of the times, in spite of the various peaceful declarations, trample human rights for economic purposes.[spa] En este trabajo de investigación se ha intentado responder a la pregunta si la teoría de la universalidad de algunos derechos, en particular aquellos de las personas indefensas, las minorías, mujeres y niños, pueda ser extendida también a los países de fe musulmana que, al contrario, insisten en la diversidad cultural. Es el caso de Túnez, el cual se ha elegido de estudiar teniendo en cuenta su pasado rico de civilizaciones y del nuevo proceso de democratización en curso, sin pasar por alto la importancia de su adhesión a los interesantes acuerdos internacionales, como el Pacto de Barcelona. Entonces se ha entendido que el obstáculo de la protección de algunos derechos no puede ser atribuido solo a la religión, ya que si las diversas religiones no existieran, no sería fácil garantizar el respeto incondicional de los derechos de los más vulnerables, en particular de aquellas minorías como las personas con discapacidad y homosexuales, que no pueden nunca convertirse, ni se convertirán, en una mayoría. Con el fin de reducir y/o eliminar estas fuertes desigualdades relacionadas con cualquier ordenamiento jurídico, incluido el país objeto de estudio, será necesario hacer de la libertad de conciencia un principio general con eficacia erga omnes y asegurar que la sociedad civil se vea reforzada y sensibilizada hacia la protección de los derechos fundamentales. Esto tendrá que suceder no solo a nivel local sino también universal, a través de un dialogo entre mayorías y minorías, bajo el signo de la verdadera democracia, superando la hostilidad de las élites políticas, que en la mayoría de los casos, detrás de las diferentes declaraciones de principios, pisotean los derechos humanos por objetivos económicos

The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associated with gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission

The proportion of different BCR-ABL1 transcript types in chronic myeloid leukemia. An international overview

There are different BCR-ABL1 fusion genes that are translated into proteins that are different from each other, yet all leukemogenic, causing chronic myeloid leukemia (CML) or acute lymphoblastic leukemia. Their frequency has never been systematically investigated. In a series of 45503 newly diagnosed CML patients reported from 45 countries, it was found that the proportion of e13a2 (also known as b2a2) and of e14a2 (also known as b3a2), including the cases co-expressing e14a2 and e13a2, was 37.9% and 62.1%, respectively. The proportion of these two transcripts was correlated with gender, e13a2 being more frequent in males (39.2%) than in females (36.2%), was correlated with age, decreasing from 39.6% in children and adolescents down to 31.6% in patients ≥ 80 years old, and was not constant worldwide. Other, rare transcripts were reported in 666/34561 patients (1.93%). The proportion of rare transcripts was associated&nbsp;with gender (2.27% in females and 1.69% in males) and with age (from 1.79% in children and adolescents up to 3.84% in patients ≥ 80 years old). These data show that the differences in proportion are not by chance. This is important, as the transcript type is a variable that is suspected to be of prognostic importance for response to treatment, outcome of treatment, and rate of treatment-free remission