Fat grafts enriched with ex-vivo expanded adipose stem cells improve hyperpigmentation of face.

Facial contour deformities associated with pigmentary changes are of major concern for plastic surgeons being difficult to treat. No definite ideal treatment option is available to address simultaneously both the contour defects as well as related hyperpigmentation. The aim of the current study is to compare long-term effects of conventional adipose tissue grafting and ex-vivo expanded ASC-enriched adipose tissue grafting for the treatment of contour deformities related pigmentary changes on the face. In this study, 80 patients of contour deformities of face with hyperpigmentation were recruited after informed consent. Two techniques, that is, conventional fat grafting (C-FG) and fat grafts enriched with expanded adipose stem cells (FG-ASCs) were used to address the pigmentation. Both techniques were explained to patients and enrolled patients were divided into two groups, that is, C-FG and FG-ASCs as per patients' choice and satisfaction. Patients of the FG-ASCs group were treated with FG-ASCs while patients of C-FGs group were treated with C-FG (without expanded ASCs). Patients were followed for 12 months and improvement in face pigmentation was assessed clinically as well as measured objectively. Patients' satisfaction was also documented as highly satisfied, satisfied, and unsatisfied. This clinical trial was registered at www.clinicaltrials.gov with ID: NTC03564808. Mean age of patients was 24.42 (±4.49), 66 patients were females. Forehead was involved in 61.20% cases, cheek in 21.20% cases, chin in 11.20% cases, and nose in 6.20% cases. In GF-ASCs group, the integrated color density was decreased (1.08 × 106 ± 4.64 × 105 ) as compared with C-FG group (2.80 × 105 ± 1.69 × 105 ). Patients treated with fat grafts enriched with expanded ASCs were significantly more satisfied as compared with patients treated with C-FG only. In conclusion, ASC-enriched autologous fat grafting is preferred option for improving the contour deformities related increased pigmentation of face skin.

Minimum criteria for defining induced mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are a promising cell type for cell-based therapies. The therapeutic potential of MSCs has been verified in preclinical and clinical studies, however; low cell number in adult tissues, restricted expansion and differentiation capacity, and donor-related heterogeneity limit their use. To address these issues, there has been considerable interest in induced pluripotent stem cells (iPSCs) derived MSCs (induced mesenchymal stem cells [iMSCs]). Investigators obtain iMSCs from iPSCs of different origins, with variable methods of generation and expansion. Results of current studies have suggested iMSCs as a unique alternative source of MSCs. However, iMSCs are defined using the same criteria (proposed previously for primary MSCs by the International Society for Cellular Therapy [ISCT]) without realizing the distinct nature of iMSCs as compared to primary MSCs. To rationally define iMSCs, additional characterization is proposed along with ISCT's minimum criteria for defining primary MSCs. Minimum criteria for defining iMSCs should include (1) spindle-shaped morphology, (2) plastic adherent growth, (3) positive expression of CD29, CD44, CD73, CD90, CD105, along with negative expression of hematopoietic markers (CD45, CD34, CD14 or CD11b, CD79α or CD19, HLA-DR), (4) lack of expression of iPSCs induction factors, (5) trilineage differentiation potential, (6) lack of ability to form teratoma, and (7) release of MSC relevant paracrine factors. Defining the minimum criteria for iMSCs will be of great interest in the field and will provide a uniform description and identification of iMSCs to expedite progress in the field. Furthermore, due to increased interest in the clinical use of iMSCs, the above-mentioned additional characterization before the clinical application is important to avoid unwanted complications for recipients.

Preenrichment with Adipose Tissue-Derived Stem Cells Improves Fat Graft Retention in Patients with Contour Deformities of the Face.

Quick absorption of adipose tissue grafts makes the outcomes less satisfactory for clinical applications. In the current study, adipose tissue grafts were mixed with adipose tissue-derived stem cells (ASCs) to improve retention of adipose tissue grafts and to make the clinical outcomes of fat grafting more reliable. Adipose tissue was either injected alone (conventional group) or mixed with ASCs (stem cell group) before injection. In both groups, adipose tissue was injected at the site of contour throughout layers of tissues till visual clinical symmetry with the opposite side was achieved. The volume of injected fat graft was measured after 72 hours and 6 months using a B-mode ultrasound device connected with a 12 MH frequency probe. The percentage reduction in the volume of injected fat, physician satisfaction scores (Ph-SCs), and patient satisfaction scores (P-SCs) were also recorded. After 6 months, there was significantly lower fat absorption in the stem cell group as compared to the conventional group. Mean physician and patient satisfaction scores were significantly improved in the stem cell group. No significant adverse effects were noted in any patient. Significantly lower absorption of graft due to the use of ASCs improves the clinical outcomes of conventional fat grafting for contour deformities of the face. The current preenrichment strategy is noninvasive, safe and can be applied to other diseases that require major tissue augmentation such as breast surgery. This trial is registered with NCT02494752.

Beyond taxol: microtubule-based treatment of disease and injury of the nervous system.

Contemporary research has revealed a great deal of information on the behaviours of microtubules that underlie critical events in the lives of neurons. Microtubules in the neuron undergo dynamic assembly and disassembly, bundling and splaying, severing, and rapid transport as well as integration with other cytoskeletal elements such as actin filaments. These various behaviours are regulated by signalling pathways that affect microtubule-related proteins such as molecular motor proteins and microtubule severing enzymes, as well as a variety of proteins that promote the assembly, stabilization and bundling of microtubules. In recent years, translational neuroscientists have earmarked microtubules as a promising target for therapy of injury and disease of the nervous system. Proof-of-principle has come mainly from studies using taxol and related drugs to pharmacologically stabilize microtubules in animal models of nerve injury and disease. However, concerns persist that the negative consequences of abnormal microtubule stabilization may outweigh the positive effects. Other potential approaches include microtubule-active drugs with somewhat different properties, but also expanding the therapeutic toolkit to include intervention at the level of microtubule regulatory proteins.

Effects of dynactin disruption and dynein depletion on axonal microtubules.

We investigated potential roles of cytoplasmic dynein in organizing axonal microtubules either by depleting dynein heavy chain from cultured neurons or by experimentally disrupting dynactin. The former was accomplished by siRNA while the latter was accomplished by overexpressing P50-dynamitin. Both methods resulted in a persistent reduction in the frequency of transport of short microtubules. To determine if the long microtubules in the axon also undergo dynein-dependent transport, we ascertained the rates of EGFP-EB3 "comets" observed at the tips of microtubules during assembly. The rates of the comets, in theory, should reflect a combination of the assembly rate and any potential transport of the microtubule. Comets were initially slowed during P50-dynamitin overexpression, but this effect did not persist beyond the first day and was never observed in dynein-depleted axons. In fact, the rates of the comets were slightly faster in dynein-depleted axons. We conclude that the transient effect of P50-dynamitin overexpression reflects a reduction in microtubule polymerization rates. Interestingly, after prolonged dynein depletion, the long microtubules were noticeably misaligned in the distal regions of axons and failed to enter the filopodia of growth cones. These results suggest that the forces generated by cytoplasmic dynein do not transport long microtubules, but may serve to align them with one another and also permit them to invade filopodia.