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Biomedical subjects

Jason L Dragoo

Publications and source records attributed to Jason L Dragoo.

7 recordsLinked to original sources

Tissue-engineered bone from BMP-2-transduced stem cells derived from human fat.

BACKGROUND: Progenitor cells capable of induction into multiple mesenchymal lineages have been isolated from human liposuction aspirates. These cells, named processed lipoaspirate cells, have previously shown in vitro osteogenic capacity. The purpose of this study was to examine the in vivo bone induction capacity of bone morphogenetic protein-2 (BMP-2)-transduced processed lipoaspirate cells using adipose tissue from multiple harvest sites. METHODS: Processed lipoaspirate cells extracted from human abdominal and buttock liposuction aspirates (n = 5) and from infrapatellar fat pads (n = 5) were placed in osteogenic media containing Dulbecco's Modified Eagle Medium with 10% fetal bovine serum supplemented with 50 muM ascorbic acid-2-phosphate and 10 mM beta-glycerol phosphate. Half of these cells were transfected with an adenovirus carrying the cDNA for bone morphogenetic protein-2 (adBMP-2). These transfected cells were then seeded onto collagen I matrices at a concentration of 2 x 10 cells/matrix and were placed into the hind limbs of severe combined immunodeficient mice (n = 10). Nontransfected processed lipoaspirate cells were placed in the contralateral limb as a control. After 6 weeks, specimens were analyzed by radiographs, densitometry, and hematoxylin and eosin and von Kossa staining. RESULTS: The average number of cells extracted from the abdominal/buttock lipoaspirates was 3.4 x 10 cells/100 ml fat aspirate and 5.5 x 10 cells per infrapatellar fat pad (average volume, 20.6 cc). All 10 BMP-2 transfected processed lipoaspirate constructs produced abundant radiographic and histologic bone. The bone was adequately mineralized and was beginning to establish a marrow cavity. There was no quantitative difference in bone production between harvest sites [mean, 2.0 +/- 0.1 aluminum units (knee) versus 2.1 +/- 0.1 aluminum units (abdomen/buttock); p = 0.14]. No bone was produced in the negative controls. CONCLUSIONS: Multipotential processed lipoaspirate cells can be extracted from adipose tissue harvested from liposuction aspirates or from the infrapatellar fat pad of the knee. Processed lipoaspirate cells can be transduced with the BMP-2 gene to produce abundant in vivo bone. These cells appear to be clinically useful for bone tissue engineering applications either as osteoprogenitor cells or as delivery vehicles for BMP-2.

Adenoviridae↗

Bacteriostatic properties of biomatrices against common orthopaedic pathogens.

Tissue-engineered grafts for tissue regeneration include either mature or progenitor cells seeded onto biomatrices that provide shape and support for developing tissue. Popular biomaterials used in orthopaedic surgery include collagen type I, hyaluronic acid, hydroxyapatite, and polylactic polyglycolic acid (PLGA). Biomatrices with bacteriostatic properties may be beneficial in promoting tissue-engineered graft survival in patients susceptible to infection. We evaluated the bacteriostatic effects of these biomaterials on the growth of the four most common orthopaedic bacterial pathogens: Staphylococcus aureus, Staphylococcus epidermidis, beta-hemolytic Streptococcus, and Pseudomonas aeruginosa. Hyaluronic acid demonstrated the largest bacteriostatic effect on these pathogens by inhibiting bacterial growth by an average of 76.8% (p = 0.0005). Hydroxyapatite and collagen inhibited growth on average by 49.7% (p = 0.011) and 37.5% (p = 0.102), respectively. PLGA exhibited the least bacteriostasis with an average inhibition of 9.8% (NS) and actually accelerated the growth of beta-hemolytic Streptococcus and P. aeruginosa.

Anti-Bacterial Agents↗

Bone induction by BMP-2 transduced stem cells derived from human fat.

PURPOSE: We have isolated pluripotent mesenchymal progenitor cells in large numbers from liposuction aspirates (processed lipoaspirate cells or PLAs). This study examines the osteogenic potential of PLAs and bone marrow aspirate cells (BMAs), when exposed to either recombinant human bone morphogenetic protein (BMP)-2 (rh-BMP-2) or adenovirus containing BMP-2 cDNA (Ad-BMP-2). METHODS: Liposuction aspirates underwent proteolytic digestion to obtain PLAs. After exposure to exogenous rh-BMP-2 or Ad-BMP-2 for four or seven days, PLAs and BMAs were assessed by histochemistry, spectrophotometry and RT-PCR. Western blotting and ELISA confirmed BMP gene transduction. Results were compared to osteoblasts and cells in osteogenic media only. PLA-Ad-BMP-2 cells were seeded on matrices and implanted in the hind limbs of SCID mice. RESULTS: Analysis of quantified bone precursor assays including extracellular ALP histomorphometry, intracellular ALP spectrophotometry, and calcified extracellular matrix (von Kossa) histomorphometry revealed that PLAs treated with exogenous rh-BMP-2 or transduced with a BMP-2 containing adenovirus (PLA-Ad-BMP-2) produced more bone precursors than osteoblasts (p=0.001). PLAs treated with exogenous rh-BMP-2 or PLA-Ad-BMP-2 also produced more bone precursors than BMAs (p=0.001), except for day 7 ALP histomorphometry (p=0.343). ELISA confirmed successful BMP-2 production by both progenitor cell groups transduced with Ad-BMP-2. H&E sections from collagen I matrices seeded with PLA-Ad-BMP-2 cells confirmed bone formation at six weeks. CONCLUSIONS: Liposuction aspirates contain PLAs that can be transfected with the BMP-2 gene, with rapid induction into the osteoblast phenotype at a rate comparable to rh-BMP-2 and osteoblast groups. Transduced PLAs produce more bone precursors with faster onset of calcified extracellular matrix than transduced BMAs. PLAs may be an ideal source of mesenchyme-lineage stem cells for gene therapy and tissue engineering.

Adenoviridae↗

Long-term results of arthroscopic resection of the distal clavicle with concomitant subacromial decompression.

PURPOSE: The goal of the study was to evaluate the long-term outcome of combined arthroscopic distal clavicle excision and subacromial decompression. TYPE OF STUDY: Retrospective, long-term cohort evaluation. METHODS: Twenty patients with an average follow-up of 6 years (range, 3.9 to 9 years) were reviewed. All patients had ipsilateral impingement syndrome and acromioclavicular joint disease at the time of surgery and underwent arthroscopic subacromial decompression combined with arthroscopic distal clavicle excision. All patients returned for evaluation in person, in addition to filling out a questionnaire incorporating the University of California, Los Angeles (UCLA), and Constant scoring systems. Preoperative and postoperative radiographs were available for all patients. RESULTS: Postoperatively, all patients had pain relief and were satisfied with the result. The average postoperative UCLA Shoulder score was 29.8 +/- 0.6, compared with 17.5 +/- 3.0 before surgery (P =.001). The Constant Shoulder score averaged 98.5 +/- 2.1 postoperatively, compared with 70.5 +/- 11.2 preoperatively (P =.001). There was 100% good to excellent results using both scoring systems. Individual components of the UCLA scoring system (pain, function, and power) all showed significant postoperative improvement (P =.001). Constant categories of pain, activities of daily living, range of motion, and power also improved. Follow-up radiographs showed maintenance of the resected distal clavicle in 19 patients. Five patients (25%) had radiographic evidence of calcific density distal to the resected clavicle but were asymptomatic. CONCLUSIONS: The long-term results of arthroscopic resection of the distal clavicle with concomitant subacromial decompression are uniformly good or excellent. Impingement and acromioclavicular joint disease frequently coexist and should be identified and treated concurrently.

Acromioclavicular Joint↗

Comparison of multi-lineage cells from human adipose tissue and bone marrow.

Our laboratory has recently characterized a population of cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multi-lineage potential similar to bone-marrow-derived mesenchymal stem cells (MSCs). This study is the first comparison of PLA cells and MSCs isolated from the same patient. No significant differences were observed for yield of adherent stromal cells, growth kinetics, cell senescence, multi-lineage differentiation capacity, and gene transduction efficiency. Adipose tissue is an abundant and easily procured source of PLA cells, which have a potential like MSCs for use in tissue-engineering applications and as gene delivery vehicles.

Adipose Tissue↗

Knee function after anterior cruciate ligament injury in elite collegiate athletes.

BACKGROUND: Anterior cruciate ligament injuries are common in athletes, but there are few studies of long-term outcomes. HYPOTHESIS: Long-term knee function of anterior cruciate ligament-injured athletes is inferior to that of their uninjured teammates. STUDY DESIGN: Retrospective cohort study. METHODS: Thirty-three Division I-A athletes who had sustained an anterior cruciate ligament injury during their college career completed a series of questionnaires that assessed knee function and quality of life 2 to 14 years after injury. Their responses were compared with those of a matched cohort of their uninjured teammates. RESULTS: There were no differences in the mean Tegner scores, modified Lysholm scores, or in the scores of the SF-36 between groups. Sixteen anterior cruciate ligament-injured athletes scored A or B in the subjective portion of the International Knee Documentation Committee score and 17 scored C or D, whereas 24 control subjects scored A or B and 9 scored C or D, a statistically significant difference between groups. Five injured and 14 control athletes had participated at a professional or national team level after college. CONCLUSIONS: Quality of life of elite collegiate athletes who sustained an anterior cruciate ligament injury was not significantly different from that of their uninjured teammates, but knee function differed between groups.

Anterior Cruciate Ligament Injuries↗

Relaxin receptors in the human female anterior cruciate ligament.

BACKGROUND: Noncontact anterior cruciate ligament injuries occur two to eight times more often in women than in men. Changes in ligament laxity and strength have been associated with female hormones such as relaxin. HYPOTHESIS: Relaxin receptors are present within the female anterior cruciate ligament. STUDY DESIGN: Controlled laboratory study. METHODS: Remnants of anterior cruciate ligament were harvested from five women and five men undergoing routine ligament reconstruction. Relaxin was biotinylated and analyzed for biologic activity with use of the mouse interpubic ligament bioassay. Immunohistochemical localization of relaxin receptors was performed with appropriate negative controls and competitive binding assays to determine receptor specificity and saturability. RESULTS: Anterior cruciate ligament sections from women but not from men showed uniform specific binding that was limited to synovial lining cells, stromal fibroblasts, and cells lining blood vessels. Specific binding was confirmed in the presence of a 2000-fold excess of human insulin, the structural homolog of relaxin, and competitive inhibition was demonstrated in the presence of a 2000-fold excess of unlabeled relaxin. CONCLUSIONS: Relaxin exhibits specific saturable binding in the female anterior cruciate ligament, where specific relaxin receptors were present. CLINICAL RELEVANCE: The high incidence of anterior cruciate ligament rupture in female athletes may be partially explained by the effects of relaxin.

Adolescent↗