Feasibility investigation of allogeneic endometrial regenerative cells.

Endometrial Regenerative Cells (ERC) are a population of mesenchymal-like stem cells having pluripotent differentiation activity and ability to induce neoangiogenesis. In vitro and animal studies suggest ERC are immune privileged and in certain situations actively suppress ongoing immune responses. In this paper we describe the production of clinical grade ERC and initial safety experiences in 4 patients with multiple sclerosis treated intravenously and intrathecally. The case with the longest follow up, of more than one year, revealed no immunological reactions or treatment associated adverse effects. These preliminary data suggest feasibility of clinical ERC administration and support further studies with this novel stem cell type.

La matriz extracelular en la curación de las heridas cutáneas. Aspectos físicos, químicos y biológicos / Extracellular matrix in healing of cutaneous wounds. Physical, chemical and biological aspects

Se revisan los nuevos conocimientos sobre la matriz extracelular (MEC), que han permitido descubrir su importante rol en la cicatrización de las heridas cutáneas. Se describen sus características morfofisiológicas y cómo interviene en la curación de las heridas cutáneas. Se presentan cuatro casos clínicos en los que se aplicó este enfoque terapéutico: los sustitutos de piel y la "cura húmeda"

We review the new knowledge about the extracellular ma-trix (ECM) that has allowed us to discover its important role in the healing of cutaneous wounds. The morpho-physiological characteristics of ECM and its role in the healing of cutaneous wounds are described. Four clinical cases are presented where this therapeutic approach was applied: the skin substitutes and the "moist wound healing".

Cadaveric bone marrow mesenchymal stem cells: first experience treating a patient with large severe burns.

BACKGROUND: In January 2005, Rasulov et al. originally published "First experience in the use of bone marrow mesenchymal stem cells (MSCs) for the treatment of a patient with deep skin burns". Here, we present the first ever treated patient with cadaveric bone marrow mesenchymal stem cells (CMSCs) in the history of Medicine. METHODS: A young man, who severely burned 60 % of his total body surface with 30 % of full-thickness burns while working with a grass trimmer that exploded, was involved in the study. MSCs were obtained from the bone marrow of a cadaver donor in a routine procurement procedure of CUCAIBA, the Province of Buenos Aires, Argentina, Ministry of Health, Transplantation Agency, cultured, expanded, and applied on the burned surfaces using a fibrin spray after early escharotomy. RESULTS: So far, our preliminary experience and our early results have been very impressive showing an outstanding safety data as well as some impressive good results in the use of CMSCs. CONCLUSIONS: Based on all this, we think that improvements in the use of stem cells for burns might be possible in the near future and a lot of time as well as many lives could be saved by many other research teams all over the world. CMSCs will probably be a real scientific opportunity in Regenerative Medicine as well as in Transplantation.

Dermal papilla cells improve the wound healing process and generate hair bud-like structures in grafted skin substitutes using hair follicle stem cells.

Tissue-engineered skin represents a useful strategy for the treatment of deep skin injuries and might contribute to the understanding of skin regeneration. The use of dermal papilla cells (DPCs) as a dermal component in a permanent composite skin with human hair follicle stem cells (HFSCs) was evaluated by studying the tissue-engineered skin architecture, stem cell persistence, hair regeneration, and graft-take in nude mice. A porcine acellular dermal matrix was seeded with HFSCs alone and with HFSCs plus human DPCs or dermal fibroblasts (DFs). In vitro, the presence of DPCs induced a more regular and multilayered stratified epidermis with more basal p63-positive cells and invaginations. The DPC-containing constructs more accurately mimicked the skin architecture by properly stratifying the differentiating HFSCs and developing a well-ordered epithelia that contributed to more closely recapitulate an artificial human skin. This acellular dermal matrix previously repopulated in vitro with HFSCs and DFs or DPCs as the dermal component was grafted in nude mice. The presence of DPCs in the composite substitute not only favored early neovascularization, good assimilation and remodeling after grafting but also contributed to the neovascular network maturation, which might reduce the inflammation process, resulting in a better healing process, with less scarring and wound contraction. Interestingly, only DPC-containing constructs showed embryonic hair bud-like structures with cells of human origin, presence of precursor epithelial cells, and expression of a hair differentiation marker. Although preliminary, these findings have demonstrated the importance of the presence of DPCs for proper skin repair.

La matriz extracelular en la curación de las heridas cutáneas. Aspectos físicos, químicos y biológicos / Extracellular matrix in healing of cutaneous wounds. Physical, chemical and biological aspects

Se revisan los nuevos conocimientos sobre la matriz extracelular (MEC), que han permitido descubrir su importante rol en la cicatrización de las heridas cutáneas. Se describen sus características morfofisiológicas y cómo interviene en la curación de las heridas cutáneas. Se presentan cuatro casos clínicos en los que se aplicó este enfoque terapéutico: los sustitutos de piel y la “cura húmeda”.

We review the new knowledge about the extracellular matrix (ECM) that has allowed us to discover its important role in the healing of cutaneous wounds. The morphophysiological characteristics of ECM and its role in the healing of cutaneous wounds are described. Four clinical cases are presented where this therapeutic approach was applied: the skin substitutes and the “moist wound healing”.

Could metabolic syndrome, lipodystrophy, and aging be mesenchymal stem cell exhaustion syndromes?

One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies.

The lysosomotropic agent, hydroxychloroquine, delivered in a biodegradable nanoparticle system, overcomes drug resistance of B-chronic lymphocytic leukemia cells in vitro.

Nonviral delivery systems are relatively easy to produce in the large scale, are safe, and elicit a negligible immune response. Nanoparticles (NPs) offer promise as nonviral vectors as biocompatible and -degradable carriers of drugs with targeting to specific sites by surface receptors of monoclonal antibodies (mAbs). We investigated the effect of four PEG-PLGA (polyethylene glycol-polylactic-co-glycolic acid) NP systems on drug-resistant B-chronic lymphocytic leukemia (B-CLL) cells in vitro, three of them encapsulating the drug, hydroxylchloroquine (HDQ), two with NP surface coatings of mAbs (NP1) CD20, (NP2) CD19, and CD20, and one (NP3) with no mAb, but tagged with the fluorescent marker, fluorescein isothiocyanate. The fourth NP system (NP4) was coated with anti-CD19/FITC and anti-CD20/Alexa-Fluor((R)) antibodies, but did not contain the active drug, HCQ. Our data indicate that PEG-PLGA nanoparticles with surface mAbs are suitable for selective drug delivery to B-CLL cells and produce a strong apoptotic effect when loaded with the lysosomotropic agent, HDQ.

Fracturas panfaciales: actualización / Panfacial fractures: update

Se hace una sucinta actualización de la epidemiología, de la anatomía y biomecánica aplicada, de la semiología y examen del paciente, de los estudios de imagen y de la terapéutica de las fracturas panfaciales.

Briefl y, to epidemiology, anatomy, bio-mechanical, semiology, patient examination, image search and therapeutic of the panfacial fractures are done

Necrosis cutánea en 30% de la superficie corporal (SCT) en recién nacido pretérmino. Presentación de una caso / Necrotizing fascitis with tissue damage over 30% of body surface area in premature neonate

Las grandes pérdidas de la cobertura cutánea y los fenómenos toxo-inflamatorios que se asocian, ya se trate de quemaduras, necrolisis tóxica epidérmica o porcesos bacterianos productores de toxinas con gran destrucción tisular, configuran una situación clínica crítica con alto riesgo de vida. Con los principios de tratamiento de grandes quemados, el control de la infección local y sistémica, el sostén clínico intensivo en una unidd de máxima complejidad y la adecuada asistencia nutricional y respiratoria se pudo tratar satisfactoriamente una fascitis necrotizante con pérdida de la cobertura cutánea en aproximadamente un 30 por ciento de la SCT causada por una infección de Estreptococo beta hemolítico grupo A en un recién nacido pretérmino (RNPT) de 1287g al nacer.