Maria Luisa Torre

Università degli Studi di Messina, Messina, Sicily, Italy

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Publications (71)172.08 Total impact

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    ABSTRACT: The aim of this work is to propose a keratinocytes (KC) culture method for clinical practice with irradiated adipose-derived mesenchymal stromal cells (ASCs) as human feeder layer, avoiding murine immortalized fibroblasts, commonly request for producing skin substitutes. ASCs were isolated, expanded, irradiated, and co-cultured with autologous or allogeneic KC. All experiments were performed using murine fibroblasts as control. Cell counts, flow cytometric analysis and ELISA were carried out, in order to define cell yield, viability and cytokine secretion. Results indicate that the optimal X-ray dose for ASCs is 120 Gy and the optimal seeding density is 625 cells/cm2; moreover, flow cytometric analysis shows that the percentage of feeder layer cells reaches values lower than 1%, within 8 days of co-culture. KC reach confluence in 6.9 days on ASCs substrate and, after confluence, the number of live cells increases again in a multilayered structure. Moreover, results show higher levels of interleukin (IL)-1a in co-culture with ASCs compared with 3T3, while no differences were observed for IL-6 and IL-8. Therefore, human ASCs enable to obtain effectively in vitro expanded KC and represent a viable alternative to murine fibroblasts for the production of clinical use skin substitutes. © 2015, The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media Dordrecht.
    Tissue Engineering and Regenerative Medicine 08/2015; 12(4):249-258. DOI:10.1007/s13770-015-0007-5 · 1.09 Impact Factor
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    ABSTRACT: In the last 30 years, encapsulation technology has been applied to different species to minimize the loss of spermatozoa after artificial insemination. In particular, the vehiculation of boar sperm cells in barium alginate membrane has proved a valid strategy to reduce the risk of polyspermy and optimize in vivo fertilizing yields. Controlled release of male gametes into the female genital tract has reduced the minimum fertilizing dose of spermatozoa. Notwithstanding these results, encapsulation has not yet reached commercial application, largely due to the additional costs of production. However, encapsulation could be useful in advanced reproductive technology, such as sex sorting, to store sorted boar semen. The controlled release of flow cytometrically sorted spermatozoa could be a promising strategy to reduce the number of cells necessary for each insemination and hence allow the widescale use of sex sorting in this species. © 2015 Blackwell Verlag GmbH.
    Reproduction in Domestic Animals 07/2015; 50 Suppl 2(S2):98-102. DOI:10.1111/rda.12538 · 1.52 Impact Factor
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    ABSTRACT: Tissue repair and regeneration is one of the major challenges of these years, aimed to restore functional and anatomical properties after traumatic, infective or degenerative diseases. New therapeutic approaches include the use of controlled delivery systems and advanced medical devices for the targeting and delivery of bioactive molecules, mesenchymal stem cells and/or growth factors, providing both the structural integrity and the biochemical information to cells when they are growing into a specific kind of tissue.
    Journal of Drug Delivery Science and Technology 05/2015; DOI:10.1016/j.jddst.2015.05.015 · 0.48 Impact Factor
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    ABSTRACT: INTRODUZIONE I pazienti adulti con deficit di GH (GHD) presentano un rischio di eventi cardiovascolari (ECV) più elevato rispetto alla popolazione generale, ma, in questo contesto clinico, vi è scarsa disponibilità di dati di letteratura riguardanti il ruolo giocato dai fattori di rischio convenzionali. Scopo di questo studio è stato quello di valutare gli ECV a lungo termine e la loro possibile relazione con fattori di rischio convenzionali come ipertensione arteriosa (IA), ipercolesterolemia ed età in pazienti adulti non diabetici con GHD programmati a ricevere terapia sostitutiva con GH (GHRT). CONCLUSIONI I dati preliminari di questo studio suggeriscono che nei pazienti adulti con GHD, non diabetici, adeguatamente sostituiti con rGH, il tasso di ECV non è dissimile da quello osservato nella popolazione generale. Nella nostra popolazione, seguita per un lungo periodo di tempo, gli eventi CV sono risultati correlati principalmente all'ipertensione arteriosa ed all'età, confermando, pertanto, la necessità di una gestione molto attenta non solo del trattamento sostitutivo con GH ma anche della pressione arteriosa in questa tipologia di pazienti.
    38° Congresso Nazionale della Società Italiana di Endocrinologia, Taormina; 05/2015

  • 05/2015; DOI:10.1530/endoabs.37.EP1137
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    ABSTRACT: With the aim of establishing the formulation of a new hydrophilic auto-gelling medical device for biomedical applications, fibroin-based microspheres were prepared. The proposed microspheres were produced by a cost-effective and industrially scalable technique, such as the spray-drying. Spray-dried silk fibroin microspheres were obtained and the effects of different hydrophilic polymer on the process yield, microsphere morphology and conformation transition of fibroin were evaluated. The final auto-gelling formulations were obtained by adding calcium gluconate (as a calcium source for alginate crosslinking) to the prepared microspheres and tested by an in vitro gelling test. This study showed that the combination of fibroin with sodium alginate and poloxamer produced the most promising auto-gelling formulation for specific biomedical applications, such as the treatment of pressure ulcers.
    Pharmaceutical Development and Technology 03/2015; DOI:10.3109/10837450.2015.1022784 · 1.20 Impact Factor
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    ABSTRACT: Mesenchymal Stromal Cells (MSC), as advanced therapy products, must satisfy all the requirements for human use of medicinal products, aiming to maintain the quality and safety of the cells. The MSC manufacturing process for clinical use should comply with the principles of Good Manufacturing Practice (GMP). This ensures that cell preparations are produced and controlled, from the collection and manipulation of raw materials, through the processing of intermediate products, to the quality controls, storage, labelling and packaging, and release. The objective of this document is to provide the minimal quality requirements for the MSC production and its delivery for clinical use, so the safety of the final cell therapy product will not be compromised. For this purpose, the document evaluates the most important steps of GMP-compliant MSC production: the isolation and expansion process; the validation phase of the process, including all quality controls for the characterization, functionality, potency and safety of MSCs; the quality control at the batch release to guarantee the safety of patient infusion. This opinion paper reflects the consensus viewpoint of the authors and scientists participating the GISM Working Group*. * GISM Working Group includes the following individual investigators: Biagi E, Del Bue M, Frigerio S, Lisini D, Marazzi M, Mareschi K, Nava S, Parolini O, Riccobon A, Romagnoli L, Viganò M.
    Stem Cells and Development 12/2014; 24(6). DOI:10.1089/scd.2014.0299 · 3.73 Impact Factor
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    ABSTRACT: This work reports on the formation of a carrier-in-carrier device for the systemic delivery and targeting of hydrophobic drugs mediated by micelle-loaded mesenchymal stromal cells (MSCs) (carrier-in-carrier) to be administered by intravenous injection. The innate ability of MSCs to reach injured tissues such as the central nervous system or other damaged tissues, is the key for the second order delivery and first order targeting. Inulin-d-alfa-tocopherol succinate micelles (INVITE M) are able to incorporate highly hydrophobic drugs and, due to their dimensions (≈7nm diameter), to penetrate the cell membrane easily and quickly. This study demonstrates that the curcumin loaded micelles (INVITE MC), sterilized by filtration, reached the maximum loading in MSCs in few minutes and that the loading was concentration-dependent. When "naked" curcumin was used, an evident cytotoxicity on MSCs was detected, while INVITE micelles protected them from this effect. Moreover, MSCs loaded with INVITE MC are able to release the entrapped drug. This study strongly supports the feasibility of the carrier-in-carrier approach for the therapy of selected diseases, i.e., this innovative drug delivery system will be proposed for the treatment of the amyotrophic lateral sclerosis (ALS). Copyright © 2014 Elsevier B.V. All rights reserved.
    Colloids and surfaces B: Biointerfaces 12/2014; 125. DOI:10.1016/j.colsurfb.2014.11.034 · 4.15 Impact Factor
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    ABSTRACT: Skin ulcers are a problem and a constant challenge, from a clinical perspective and because of their social and economic implications, because of the high number of patients, the difficulties of healing and the long treatment times, which inevitably imply higher costs. In order to improve these aspects, it is essential to lay down guidelines or specific diagnostic-therapeutic procedures, which can consider the skin lesion in context and can standardise action plans, 'which are too often discordant or in conflict. In this context, the prevention and treatment of infection is an important starting point to encourage the repair process, which must be associated with careful cleansing and pain treatment and, in some cases, reconstructive surgery. Where dressings are concerned, the best results in terms of healing - both shorter healing times and a better outcome - are achieved thanks to the innovative principles of regenerative medicine, which relies on the combined use of advanced dressings and tissue engineering products. The former create an excellent environment for the healing process, while the latter interact and stimulate the various stages of repair.
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    ABSTRACT: Aim. The aim of the study was to evaluate the short-term impact and safety of a non-ablative bipolar radiofrequency device in the treatment of face skin. Methods. A randomized study was carried out on 62 healthy subjects with a standard age-related level of skin laxity, subdivided into two groups. One group received a single treatment with X-2© device and the second received three treatments by the same device on a monthly base. Clinical improvements of the treated areas were detected by collecting photographic documentation pre- and post-treatments and measuring skin parameters such as total water content, elasticity and sebum levels at baseline, and 1 hour after the last treatment. Results. Data showed significant effect of radiofrequency treatment on skin hydration, skin elasticity and on sebum. No interaction effect was noted between age parameter and treatment on skin hydration and elasticity: this indicates a substantial positive effect independently on age of subjects. Conclusion. The results suggest that the radiofrequency treatment improves subjective and objective judgments of patients and doctors as well as some skin quality parameters and it can be considered a useful tool to improve skin in terms of elasticity in the field of non invasive technologies.
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    ABSTRACT: Aryl hydrocarbon Receptor (AHR) pathway has a key-role in cellular detoxification mechanisms and seems implicated in tumorigenesis. Moreover, polymorphisms and mutations of AHR gene have been associated with several human and animal tumours. Although AHR has been found differently expressed in pituitary adenomas, AHR gene mutation status has never been investigated in acromegalic patients. In this study we evaluated patients with apparently sporadic GH-secreting pituitary adenoma for AHR gene variants. 70 patients with sporadic GH-secreting pituitary adenoma (M=27, age 59.1±1.6 years) and 157 sex- and age-matched controls were enrolled in the study. In all patients and controls, the exons 1, 2, 3, 5 and 10 of AHR gene were evaluated for nucleotide variants by sequencing analysis. The rs2066853 polymorphism was identified in the exon 10 of 18/70 acromegalic patients and 9/157 healthy subjects (25.7 vs. 5.7%, χ(2) 18.98 p <0.0001), in homozygosis in one patient and in heterozygosis in the other 17 and in the 9 healthy subjects. Moreover, a heterozygous rs4986826 variant in exon 10 was identified in a patient with heterozygous rs2066853 polymorphism, and in the patient with homozygous rs2066853 variant. This second polymorphism was not detected in the control group. Patients with rs2066853 polymorphism showed increased IGF-1 ULN (p <0.05) and prevalence of cavernous sinus invasion (p <0.05), thyroid (p 0.02), bladder (p 0.0001) or lymphohematopoietic (p <0.05) tumours. AHR gene rs2066853 polymorphism is significantly more frequent in acromegalic patients than in healthy subjects, regardless of gender, pituitary tumour size, age at diagnosis and prevalence of colonic tumours and is associated with increased disease aggresivity. Moreover, the rs4986826 variant was detected in few patients with rs2066853 polymorphism, but its role is to be cleared. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 02/2014; 81(2). DOI:10.1111/cen.12424 · 3.46 Impact Factor
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    ABSTRACT: Chronic wounds are an expression of underlying complex pathologies and have a high incidence. Skin substitutes may represent an alternative approach to treat chronic ulcers. The aim of this retrospective observational study was to evaluate the wound reduction using skin substitutes based on allogenic fibroblasts or keratinocytes in 30 patients not responding to conventional therapy. Wound bed was prepared, then keratinocytes on Laserskin(®) to treat superficial wounds or fibroblasts on Hyalograft 3D(R) to treat deep leg ulcers were applied, and finally wounds were treated with a secondary dressing composed of nanocrystalline silver. Once a week constructs were removed and new bioengineered products were applied, as well as nanocrystalline silver medication. In none of the cases under examination did any complications arise relating to the treatment. We also achieved a reduction in wound dimension and exudates, and an increase in wound bed score. Postoperative assessment shows a degree of healing that is statistically higher in the group treated with keratinocytes as compared with the fibroblast group. This retrospective study improves our understanding and defines the clinical indications for the various uses of the two types of skin substitutes.
    International Wound Journal 02/2014; DOI:10.1111/iwj.12223 · 2.15 Impact Factor
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    ABSTRACT: Prediction of ischemic cardiovascular events (ICE) in acromegalic patients stratified accordingly with Framingham (FS) and Agatston score (AS). 32 patients with active (group A 0) and 20 with controlled (group B 0) acromegaly have been enrolled. During the 5-year follow-up, 19 out of 32 patients in group A 0 reached disease control. At entry, FS and AS, by an eight-slice MDCT scanner, were calculated in all patients. ICE were diagnosed by autopsy, if lethal, and by electrocardiography and/or echocardiography, if non-lethal. Overall, 9.6 % of patients died for lethal ICE. AS >400, but not high FS at entry, was associated with increased risk of lethal ICE. Lethal ICE had occurred in two patients of group A 0 and three of group B 0 (p NS), while a non-lethal ICE had occurred in two cases of the former and in other two of the latter group (p NS). Either FS or AS was correlated with the risk for ICE overall (p < 0.02), but only AS correlated with that of lethal ICE (p < 0.0003). Survival analysis demonstrated reduced life expectancy in patients with high FS (p < 0.02). In acromegalics, AS >400 is associated with increased risk of lethal ICE, while high FS is associated with reduced life expectancy, regardless of disease control.
    Endocrine 11/2013; 47(1). DOI:10.1007/s12020-013-0115-8 · 3.88 Impact Factor
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    ABSTRACT: Skin substitutes are epidermal, dermal or complete bilayered constructs, composed by natural or synthetic scaffolds and by adherent cells such as fibroblasts, keratinocytes or mesenchymal stem cells. Silk fibroin is a promising polymer to realize scaffolds, since it is biocompatible, biodegradable, and exhibits excellent mechanical properties in terms of tensile strength. Moreover, fibroin can be added of others components in order to modify the biomaterial properties for the purpose. The aim of this work is to prepare silk fibroin films for adipose-derived stem cell (ADSCs) culture as a novel feeder layer for skin tissue engineering. Pectin has been added to promote the protein conformational transition and construct strength, while glycerol as plasticizer, providing biomaterial flexibility. Eighteen formulations were prepared by casting method using fibroin, pectin (range 1-10% w/w), and glycerol (range 0-20% w/w); films were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry assay, to select the optimal composition. A stable fibroin conformation was obtained using 6% w/w pectin, and the best mechanical properties were obtained using 12% w/w glycerol. Films were sterilized, and human ADSCs were seeded and cultured for 15 days. Cells adhere to the support assuming a fibroblastic-like shape and reaching confluence. The ultrastructural analysis evidences typical active-cell features and adhesion structures that promote cell anchorage to the film, thus developing a multilayered cell structure. This construct could be advantageously employed in cutaneous wound healing or where the use of ADSCs scaffold is indicated either in human or veterinary field.
    International journal of immunopathology and pharmacology 09/2013; 26(1 Suppl):43-9. · 1.62 Impact Factor
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    ABSTRACT: Acromegalic patients have a higher risk of developing colorectal tumours (CRT). The common C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene is a well-documented CRT risk factor in the general population, but its role in acromegaly has never been examined. We investigated the influence of MTHFR C677T polymorphism, folate status and other lifestyle, nutritional and disease-specific variables on CRT risk in acromegaly. Clinical data were collected from 115 acromegalic patients (25 with active disease) who underwent a complete colonoscopy. C677T MTHFR genotype, homocysteine, vitamin B12, insulin growth factor and insulin levels, as well as metabolic variables were evaluated. Colorectal tumours were identified in 51 patients (3 adenocarcinomas). MTHFR C677T distribution was in the Hardy-Weinberg equilibrium and similar in patients with or without CRT. There was a correlation between patients with TT genotype and CRT occurrence (Spearman's test: P = 0.03), with an Odds Ratio (OR) of 1.32 (95 % CI 0.522-3.362, P NS). A folate-MTHFR genotype interaction on CRT risk was found (P = 0.037): in the lower folate subgroup, TT patients showed a 2.4 higher OR for CRT (95 % CI 0.484-11.891; P NS) than C-allele carriers. Smoking (P = 0.007), increased HbA1c levels (P = 0.021), dyslipidaemia (P = 0.049), acromegaly control (P = 0.057), and folate-MTHFR genotype interaction (P = 0.088) were associated with CRT at multivariate analysis. In this cohort of acromegalic patients, CRT risk is increased in 677TT MTHFR patients with low plasma folate levels. Smoking, high HbA1c levels, dyslipidaemia and disease activity were also associated with increased CRT risk.
    Pituitary 06/2013; 17(3). DOI:10.1007/s11102-013-0499-8 · 3.20 Impact Factor
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    ABSTRACT: A routine use of boar-sexed semen is limited by the long sorting time necessary to obtain an adequate number of sexed spermatozoa for artificial insemination and by the high susceptibility of spermatozoa of this species to damages induced by sorting procedure and subsequent cryopreservation. The aim of this work was to study the impact of encapsulation in barium alginate membrane on sorted boar spermatozoa by evaluating membrane integrity, chlortetracycline staining patterns, protein tyrosine phosphorylation, and Hsp70 immunolocalization during storage over 72 hours in liquid or encapsulated form. The encapsulation procedure significantly (P < 0.05) decreased the overall membrane integrity of control unsorted semen (81.8 vs. 57.4, CTR vs. CPS), but did not negatively affect the overall viability and the chlortetracycline staining patterns of sorted encapsulated cells. Moreover, encapsulation significantly decreased (P < 0.05) the overall phosphotyrosin A pattern cell percentage in unsorted (98.4 vs. 92.6, CTR vs. CPS) but not in sorted semen (64.0 vs. 74.2; SORT CTR vs. SORT CPS). As for Hsp70, the overall percentage of cells displaying the different patterns was significantly influenced (P < 0.05) by treatment but not by storage time. The sorting procedure seems to induce the major changes, whereas encapsulation tends to exert a protective effect on sorted semen by increasing the percentage of spermatozoa displaying the T pattern (2.8 vs. 24.3; SORT CTR vs. SORT CPS). In conclusion, our data confirm that the damaging impact of the encapsulation in barium alginate capsules seems to be limited when compared with that of the sorting procedure and, moreover, the association of the two procedures does not result in an algebraic sum of the negative effects. These results suggest the possibility of a future utilization of the encapsulation technology in order to store sorted spermatozoa and permit their controlled release in the female genital tract.
    Theriogenology 06/2013; 80(5). DOI:10.1016/j.theriogenology.2013.05.018 · 1.80 Impact Factor
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    ABSTRACT: The ligand/receptor hepatocyte growth factor (HGF)/c-met signaling system promotes cellular growth and angiogenesis through PI3K/phosphor-Akt and STAT3/phosphor-STAT3 downstream effectors. In this study, we have evaluated the expression of molecules of the HGF/c-met pathway in pituitary adenomas (PA). The expression of HGF, c-met, PI3K (p85αsubunit) pAkt, STAT3, and pSTAT3 was analyzed by immunohistochemistry in an archival series of 30 PA (12 non-functioning and 18 functioning; 25 macroadenomas and 5 microadenomas). PAs expressed all six proteins in tumor epithelial cells. The proportion of c-met(+ve) cells was greater than HGF(+ve) cells (49 ± 19 vs 34 ± 17 %, P < 0.01), the pAkt(+ve) cells greater than PI3K(+ve) cells (39 ± 16.0 vs 1.3 ± 0.5 %, P < 0.001), and the STAT3(+ve) cells greater than active pSTAT3(+ve) cells (14 ± 8 vs 7 ± 6 %, P < 0.01). Furthermore, endothelial Akt immunostaining was detected on the vascular surface area of 17 PAs, in macroadenomas more frequently than in microadenomas (82 vs 18 %). The percentage of immunostained endothelial cells was greater in macro than in microadenomas (19 ± 7 and 7 ± 3 %; P < 0.05). In conclusion, HGF and c-met are widely expressed in PA, and correlate with pAkt expression. These data, together with the finding of pAkt immunostaining on microvascular areas related to tumor size, suggest a major role of the pAKT signaling in tumor growth and angiogenesis. There might be practical implications for the targeted therapy of PA.
    Endocrine 04/2013; 44(3). DOI:10.1007/s12020-013-9950-x · 3.88 Impact Factor
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    ABSTRACT: Some biological properties of Bombyx mori sericins from twenty strains were investigated, fourteen fed with artificial diet, two with fresh mulberry leaves and four with both diets. Sericin exhibited ROS-scavenging, anti-tyrosinase and anti-elastase properties, the strain significantly influencedthese properties, while diet only influenced the anti-tyrosinase activity. Sericins were clustered into 5 groups and one sericin from each group was further studied: sericins showed anti-proliferative activity on in vitro stimulated peripheral blood mononuclear cells; some strains decreased in vitro secretion of IFNγ, while no effects were observed on TNFα and IL10 release. Therefore, a mixture of sericins extracted from the most promising strains may be useful for dermatological and cosmetic use.
    International journal of biological macromolecules 03/2013; 58. DOI:10.1016/j.ijbiomac.2013.03.054 · 2.86 Impact Factor
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    ABSTRACT: Abstract Extracts of Crataegus monogyna Jacq. (hawthorn) show an interesting free radical scavenging (FRS) effect, related to their flavonoids content. Unfortunately, their oral administration is affected by their low bioavailability. The aim of this work is to obtain a multiparticulate drug delivery system for hawthorn extracts for oral administration. The extracts from flowering tops (FL) or fruits (FR) of hawthorn were obtained with maceration, using ethanol as an extraction solvent, and their antioxidant activity was evaluated. FL extract showed the highest FRS activity (EC(50) 3.72 ± 1.21 µg/ml), so it was selected to prepare microparticulate systems by a spray-drying technique, which were characterized by granulometric analysis, scanning electron microscopy-energy dispersive X-ray spectroscopy, confocal fluorescence microscopy and hyperoside content. Antioxidant activity was evaluated before and after gastrointestinal transit in vitro simulation. Results indicate that the microparticulate systems maintained the antioxidant activity of hawthorn also after gastrointestinal transit in vitro simulation, exhibiting properties suitable for oral administration.
    Pharmaceutical Development and Technology 01/2013; 19(1). DOI:10.3109/10837450.2012.752387 · 1.20 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects.
    Current pharmaceutical design 12/2012; 19(13). DOI:10.2174/1381612811319130015 · 3.45 Impact Factor

Publication Stats

874 Citations
172.08 Total Impact Points


  • 2007-2014
    • Università degli Studi di Messina
      • Dipartimento di Medicina Clinica e Sperimentale
      Messina, Sicily, Italy
  • 1993-2014
    • University of Pavia
      • Department of Drugs Sciences
      Ticinum, Lombardy, Italy
  • 2012
    • University of Naples Federico II
      Napoli, Campania, Italy
    • University of Bologna
      • Department of Veterinary Medical Sciences DIMEVET
      Bolonia, Emilia-Romagna, Italy
  • 2002-2010
    • University of Milan
      • • Department of Biomedical Science
      • • Faculty of Veterinary Medicine
      Milano, Lombardy, Italy
    • Università degli Studi di Salerno
      • Department of BioMedical and Pharmaceutical Sciences FARMABIOMED
      Salerno, Campania, Italy