Sustained clinical improvement of Parkinson's disease in two patients with facially-transplanted adipose-derived stromal vascular fraction cells.

Cell-based therapy has been studied as an alternative for Parkinson's Disease (PD), with different routes of administration. The superficial fascia and facial muscles possess a rich blood supply, while venous and lymphatic access via the orbit and the cribriform plate provide a route to cerebral circulation. We here document positive clinical effects in two patients with PD treated with autologous adipose-derived stromal vascular fraction (SVF) cell preparation, implanted into the face and nasal cavity. Two patients with PD were transplanted with 60 million total nucleated cells in processed SVF into the facial muscles and nose. Serial evaluations were carried out up to 5 years (patient 1) and 1 year (patient 2), using the PDQ-39, the UPDRS, and serial videos. Video scoring was reviewed in a blinded fashion. Both patients reported qualitative improvement in motor and nonmotor symptoms following injection. Quantitatively, PDQ-39 scores decreased in all categories for both. On-medication UPDRS motor scores decreased in both (20 to 4 in patient 1, 18 to 3 in patient 2) despite taking the same or less medication (LEDD 350 to 350 in patient 1, LEDD 1175 to 400 in pt2). Both subjects had off-medication UPDRS scores similar to their pretreatment on-medication scores (20 to 14 in patient 1, 18 to 23 in patient 2). These preliminary findings describe local facial and nasal injections of SVF preparation followed by prolonged clinical benefit in two patients. Despite an unknown mechanism of action, this potential therapy warrants careful verification and investigation.

Intra-articular infiltration of adipose-derived stromal vascular fraction cells slows the clinical progression of moderate-severe knee osteoarthritis: hypothesis on the regulatory role of intra-articular adipose tissue.

BACKGROUND: The infiltration of the stromal vascular fraction (SVF) of autologous adipose tissue to treat osteoarthritis has been used for several years demonstrating its safety and noticeable efficacy. This article presents clinical data from patients afftected by moderate and severe knee osteoarthritis demonstrating safety and clinical efficacy of the treatment when this autologous cell product is injected in the knee joint and patients evaluated post-operatively after 1 year. However, what do we know about the mechanism that underlies this clinical improvement? This article proposes, for the first time in our opinion, a hypothesis of the mode of action that involves structural and molecular interactions between SVF and infrapatellar fat pad (IFP). As consequence, there would be a re-education of intra-articular adipose tissue, which we consider a key player for the clinical effect observed in the mid and long term mainly due to immuno-regulatory mechanisms. METHODS: This is a retrospective and not controlled study that evaluated 50 patients (100 joints) ranging from 50 to 89 years old, separated by age cohorts. Clinical efficacy was assessed using the Lequesne, WOMAC, and VAS scales, by ultrasound control and quantification of the biochemical profiles of synovial fluid. RESULTS: There were no serious adverse effects. All the indexes studied showed a significant clinical improvement after 1-year follow-up for all ages and OA degree groups. This finding was correlated with the ultrasound observations and biochemical data, which show a marked decrease in catabolic and pro-inflammatory molecules (MMP-2, IL-1B, IL-6, and IL-8) and significant increase for anabolic and anti-inflammatory molecules (IGF-1 and IL-10). CONCLUSIONS: We conclude that intra-articular SVF infiltration for knee OA treatment is safe and effective during 1 year. We propose that applied SVF cells cause a cascade of molecular and structural events that, through complex interactions between IFP and SVF, re-educating the intra-articular fatty tissue towards a homeostatic, protective, and anti-inflammatory function, which will ultimately promote the restructuring and regeneration of damaged tissues.

Reproducible Volume Restoration and Efficient Long-term Volume Retention after Point-of-care Standardized Cell-enhanced Fat Grafting in Breast Surgery.

UNLABELLED: Lipoaspirated fat grafts are used to reconstruct volume defects in breast surgery. Although intraoperative treatment decisions are influenced by volume changes observed immediately after grafting, clinical effect and patient satisfaction are dependent on volume retention over time. The study objectives were to determine how immediate breast volume changes correlate to implanted graft volumes, to understand long-term adipose graft volume changes, and to study the "dose" effect of adding autologous stromal vascular fraction (SVF) cells to fat grafts on long-term volume retention. METHODS: A total of 74 patients underwent 77 cell-enhanced fat grafting procedures to restore breast volume deficits associated with cosmetic and reconstructive indications. Although all procedures used standardized fat grafts, 21 of the fat grafts were enriched with a low dose of SVF cells and 56 were enriched with a high SVF cell dose. Three-dimensional imaging was used to quantify volume retention over time. RESULTS: For each milliliter of injected fat graft, immediate changes in breast volume were shown to be lower than the actual volume implanted for all methods and clinical indications treated. Long-term breast volume changes stabilize by 90-120 days after grafting. Final volume retention in the long-term was higher with high cell-enhanced fat grafts. CONCLUSIONS: Intraoperative immediate breast volume changes do not correspond with implanted fat graft volumes. In the early postoperative period (7-21 days), breast volume increases more than the implanted volume and then rapidly decreases in the subsequent 30-60 days. High-dose cell-enhanced fat grafts decrease early postsurgical breast edema and significantly improve long-term volume retention.

Signaling pathways involved in antidepressant-induced cell proliferation and synaptic plasticity.

In the last years it has been proposed that the antidepressant action is mediated not only by changes in monoamine levels but also in association with modifications involving cell proliferation and plasticity in some brain limbic areas as hippocampus, and also frontal cortex and amygdala. This leads to the merging of the classic "monoaminergic hypothesis of depression", with the newer "neurotrophic hypothesis of depression". Here we review two important signaling pathways: the Wnt/ß-catenin pathway -implicated in cellular proliferation and synaptic plasticity- that is downregulated in major depression and upregulated after antidepressant treatment; and the mTOR pathway -controling synaptic plasticity- recently related to present disrupted functioning in major depression, and as the target of some drugs with fast-acting potential antidepressant action. These pieces of evidences are confirmed in a variety of animal models of depression and are predictive of antidepressant actions. We also review the role of another two important neurotrophic factors: brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) that mediate the antidepressant effects. All of the above intracellular pathways interact by a crosstalk mediated by Akt, a key regulator molecule that may underlie the fine tuning between proliferative and neuroplasticity changes induced by antidepressant drugs.

Functional autoradiography and gene expression analysis applied to the characterization of the alpha2-adrenergic system in the chicken brain.

Here we report a functional autoradiographic study of [(35)S]GTPgammaS binding induced by alpha(2)-adrenoceptor activation in chicken brain tissue sections using both 10(-4)M UK 14304 (bromoxidine or brimonidine) and 10(-6)M epinephrine as alpha(2)-adrenoceptor agonists. Assays were performed using two different incubation buffers: glycylglycine or Tris-HCl. Changes in the [(35)S]GTPgammaS basal binding values were detected, and different [(35)S]GTPgammaS specific binding values were also obtained depending on the buffer used for each drug. The best results were obtained with epinephrine in Tris-HCl, with slightly higher stimulation values than the observed with UK 14304 in glycylglycine buffer. The effect of the addition of adenosine deaminase to the incubation buffer was also tested. This effect decreasing basal binding in chicken was very small when compared to mammals, according with differences found in adenosine 1 receptor expression levels. Structures presenting alpha(2)-adrenoceptor-mediated G(i/o) protein stimulation fitted with areas previously described as enriched in alpha(2)-adrenoceptors in chicken brain, and their homologous areas in mammals. These data confirm the specificity of the results and reinforce the implication of the alpha(2)-adrenoceptors in the function of these brain nuclei. On the other hand, the expression level of the different alpha(2)-adrenoceptor subtypes was tested with real-time PCR. Contrasting with the alpha(2)-adrenoceptor subtype distribution previously described with radioligand competition assays, where alpha(2A) was the predominant alpha(2)-adrenoceptor subtype (>/=75%); in the present work, the ratio of alpha(2A):alpha(2B/C) gene expression was lower than expected both in telencephalon, tectum opticum, and cerebellum.