Brian E. Grottkau

Adipose stem cells originate from perivascular cells

Recent research has shown that adipose tissues contain abundant MSCs (mesenchymal stem cells). The origin and location of the adipose stem cells, however, remain unknown, presenting an obstacle to the further purification and study of these cells. In the present study, we aimed at investigating the origins of adipose stem cells. α‐SMA (α‐smooth muscle actin) is one of the markers of pericytes. We harvested ASCs (adipose stromal cells) from α‐SMA‐GFP (green fluorescent protein) transgenic mice and sorted them into GFP‐positive and GFP‐negative cells by FACS. Multilineage differentiation tests were applied to examine the pluripotent ability of the α‐SMA‐GFP‐positive and ‐negative cells. Immunofluorescent staining for α‐SMA and PDGF‐Rβ (platelet‐derived growth factor receptor β) were applied to identify the α‐SMA‐GFP‐positive cells. Then α‐SMA‐GFP‐positive cells were loaded on a collagen—fibronectin gel with endothelial cells to test their vascularization ability both in vitro and in vivo. Results show that, in adipose tissue, all of the α‐SMA‐GFP‐positive cells congregate around the blood vessels. Only the α‐SMA‐GFP‐positive cells have multilineage differentiation ability, while the α‐SMA‐GFP‐negative cells can only differentiate in an adipogenic direction. The α‐SMA‐GFP‐positive cells maintained expression of α‐SMA during multilineage differentiation. The α‐SMA‐GFP‐positive cells can promote the vascularization of endothelial cells in three‐dimensional culture both in vitro and in vivo. We conclude that the adipose stem cells originate from perivascular cells and congregate around blood vessels.

Bone marrow derived pluripotent cells are pericytes which contribute to vascularization.

Pericytes are essential to vascularization, but the purification and characterization of pericytes remain unclear. Smooth muscle actin alpha (α-SMA) is one maker of pericytes. The aim of this study is to purify the α-SMA positive cells from bone marrow and study the characteristics of these cells and the interaction between α-SMA positive cells and endothelial cells. The bone marrow stromal cells were harvested from α-SMA-GFP transgenic mice, and the α-SMA-GFP positive cells were sorted by FACS. The proliferative characteristics and multilineage differentiation ability of the α-SMA-GFP positive cells were tested. A 3-D culture model was then applied to test their vascularization by loading α-SMA-GFP positive cells and endothelial cells on collagen-fibronectin gel. Results demonstrated that bone marrow stromal cells are mostly α-SMA-GFP positive cells which are pluripotent, and these cells expressed α-SMA during differentiation. The α-SMA-GFP positive cells could stimulate the endothelial cells to form tube-like structures and subsequently robust vascular networks in 3-D culture. In conclusion, the bone marrow derived pluripotent cells are pericytes and can contribute to vascularization.

γ-secretase inhibitor induces adipogenesis of adipose-derived stem cells by regulation of Notch and PPAR-γ

Objective:  To determine the inhibitory effect and mechanism of Notch signalling on adipogenesis of mouse adipose‐derived stem cells (mASCs).

Segmental Lumbar Rotation in Patients with Discogenic Low Back Pain During Functional Weight-Bearing Activities

BACKGROUND Little information is available on vertebral motion in patients with discogenic low back pain under physiological conditions. We previously validated a combined dual fluoroscopic and magnetic resonance imaging system to investigate in vivo lumbar kinematics. The purpose of the present study was to characterize mechanical dysfunction among patients with confirmed discogenic low back pain, relative to asymptomatic controls without degenerative disc disease, by quantifying abnormal vertebral motion. METHODS Ten subjects were recruited for the present study. All patients had discogenic low back pain confirmed clinically and radiographically at L4-L5 and L5-S1. Motions were reproduced with use of the combined imaging technique during flexion-extension, left-to-right bending, and left-to-right twisting movements. From local coordinate systems at the end plates, relative motions of the cephalad vertebrae with respect to caudad vertebrae were calculated at each of the segments from L2 to S1. Range of motion of the primary rotations and coupled translations and rotations were determined. RESULTS During all three movements, the greatest range of motion was observed at L3-L4. L3-L4 had significantly greater motion than L2-L3 with left-right bending and left-right twisting movements (p < 0.05). The least motion occurred at L5-S1 for all movements; the motion at this level was significantly smaller than that at L3-L4 (p < 0.05). Range of motion during left-right bending and left-right twisting at L3-L4 was significantly larger in the degenerative disc disease group than in the normal group. The range of motion at L4-L5 was significantly larger in the degenerative group than in the normal group during flexion; however, the ranges of motion in both groups were similar during left-to-right bending and left-to-right twisting. CONCLUSIONS The greatest range of motion in patients with discogenic back pain was observed at L3-L4; this motion was greater than that in normal subjects, suggesting that superior adjacent levels developed segmental hypermobility prior to undergoing fusion. L5-S1 had the least motion, suggesting that segmental hypomobility ensues at this level in patients with discogenic low back pain.

Osteogenesis of Adipose-Derived Stem Cells.

Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells (ASCs) has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction.

Polymeric nanoparticles for a drug delivery system.

In recent years, nanotechnology research has made great strides in the area of pharmacy, especially for drug delivery systems. Polymeric nanoparticles provide significant stability in anti-neoplastic drug research and have demonstrated the ability to solve the problems of therapeutic efficacy and diagnostic sensitivity. In this review, we describe the specific advantages of polymeric nanoparticles and their applications for a drug delivery system. The latest research on PHA-based polymeric nanoparticles and PLGA is also discussed.

Costello syndrome: orthopaedic manifestations and functional health.

Sixteen individuals with Costello syndrome underwent a complete history, physical examination, and medical record review. Medical history and record review were performed for two additional children with Costello syndrome. The POSNA Functional Health Outcome Questionnaire Baseline Assessment was completed by the parents of all 18 children. All the children were below the fifth percentile for height and all had ligamentous laxity. All children demonstrated delayed walking and none was able to run. Orthopaedic problems included tight heel cords, congenital vertical talus, planovalgus feet, hip subluxation, kyphosis, scoliosis, radial head subluxation, elbow flexion deformity, reduced shoulder range of motion, and limitation of overhead activity. Foot problems were most frequently encountered. Two children had no orthopaedic symptoms. All children with Costello syndrome had poor scores on the POSNA Functional Health Outcome Questionnaire. Orthopaedic problems are a significant part of Costello syndrome, and affected individuals should be evaluated and followed-up regularly by an orthopaedic surgeon.

Multilineage Differentiation of Dental Pulp Stem Cells from Green Fluorescent Protein Transgenic Mice

AimThe aim of this study was to confirm the multilineage differentiation ability of dental pulp stem cells (DPSCs) from green fluorescent protein (GFP) transgenic mice. The expression of GFP in DPSCs was also observed during differentiation.MethodologyDPSCs were harvested from the dental pulp tissue of transgenic nude mice, and then transferred to osteogenic, adipogenic, and chondrogenic media. The morphological characterization of induced cells was observed by microscopy and histological staining. The expression of marker genes was measured by RT‐PCR.ResultsThe endogenous GFP and multilineage potential of transgenic DPSCs had no influence on each other. Moreover, the results of fluorescence microscopic imaging suggest that there was no significant decline of GFP expression during DPSCs differentiation.ConclusionAs the population of GFP labeled DPSCs can be easily identified, this will be a promising method for tracking DPSCs in vivo.

Current concepts in the treatment of hallux valgus.

Hallux valgus is a common disorder of the forefoot that results from medial deviation of the first metatarsal and lateral deviation and/or rotation of the great toe (hallux) with or without medial soft-tissue enlargement of the first metatarsal head (bunion). It is the most common pathologic condition affecting the great toe. There is a known predilection of hallux valgus and bunions in the female population (female–male ratio =9:1), which is likely due to both biomechanics (joint laxity/instability) and shoe wear demands. There are many different conservative and surgical treatment options for hallux valgus and bunions. The multitude of established procedures and technique modifications in the literature underscores the fact that no single approach universally addresses this common disorder.

Multidetector computed tomography of pediatric lateral condylar fractures.

The objective of this study was to compare lateral condylar fracture characterization using radiographs and multidetector computed tomography (MDCT) of the elbow and to evaluate outcomes in a group of children managed based on MDCT findings. Methods: Unenhanced MDCT of the elbow with sagittal and coronal reformations was prospectively performed without sedation in 10 children between 1 and 16 years of age with lateral condylar fractures identified on frontal and lateral radiographs of the elbow. Two blinded readers reviewed all radiographs and MDCT images independently and in consensus. For the radiographs and MDCT images, readers graded the displacement of the lateral condyle fracture fragment and classified the fractures according to the Milch classification. Articular and epiphyseal cartilage integrity was assessed on MDCT. Patients were managed based on the consensus interpretation of the MDCT study. The frequency of interobserver agreement, discordant grading of fracture displacement and fracture classification between radiographs and MDCT images, and altered management based on the MDCT findings were determined. Results: Individual readers agreed on fracture displacement in 9 patients (90%) on radiographs and in all 10 patients (100%) on MDCT. Individual readers agreed on fracture classification in 4 patients (40%) on radiographs and in 9 patients (90%) on MDCT. In 4 patients (40%), grading of fracture displacement differed between the consensus interpretation of the radiographs and MDCT images. In 6 patients (60%), fracture classification differed between the consensus interpretation of the radiographs and MDCT images. All 3 patients with fracture displacement greater than 5 mm and 1 patient with fracture displacement between 2 and 5 mm demonstrated disruption of the articular and epiphyseal cartilage on MDCT. Two patients (20%) with fracture displacement near the surgical threshold of 2 mm had altered management based on the MDCT findings. All patients progressed to complete fracture healing, with no delayed displacement or other complications. Conclusions: Multidetector computed tomography is a highly reproducible means of characterizing pediatric lateral condylar fractures and frequently demonstrates disruption of the epiphyseal and articular cartilage in patients with fracture displacement greater than 2 mm. The findings of MDCT may lead to altered treatment in patients with fracture displacement near the surgical threshold of 2 mm.