Mesenchymal Progenitor Cells and Their Orthopedic Applications: Forging a Path towards Clinical Trials

Mesenchymal progenitor cells (MPCs) are nonhematopoietic multipotent cells capable of differentiating into mesenchymal and nonmesenchymal lineages. While they can be isolated from various tissues, MPCs isolated from the bone marrow are best characterized. These cells represent a subset of bone marrow stromal cells (BMSCs) which, in addition to their differentiation potential, are critical in supporting proliferation and differentiation of hematopoietic cells. They are of clinical interest because they can be easily isolated from bone marrow aspirates and expanded in vitro with minimal donor site morbidity. The BMSCs are also capable of altering disease pathophysiology by secreting modulating factors in a paracrine manner. Thus, engineering such cells to maximize therapeutic potential has been the focus of cell/gene therapy to date. Here, we discuss the path towards the development of clinical trials utilizing BMSCs for orthopaedic applications. Specifically, we will review the use of BMSCs in repairing critical-sized defects, fracture nonunions, cartilage and tendon injuries, as well as in metabolic bone diseases and osteonecrosis. A review of www.ClinicalTrials.gov of the United States National Institute of Health was performed, and ongoing clinical trials will be discussed in addition to the sentinel preclinical studies that paved the way for human investigations

Lysophosphatidic Acid Acyltransferase β (LPAATβ) Promotes the Tumor Growth of Human Osteosarcoma

Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2) in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated.Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma.Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This is especially attractive given the availability of selective pharmacological inhibitors

Patient-subjective cosmetic outcomes following the varying stages of tissue expander breast reconstruction: The importance of completion

a b s t r a c t Introduction: Tissue expander breast reconstruction consists of three major surgical steps: placement of the expander after mastectomy, exchange of the expander for an implant, and nipple-areola complex reconstruction. The evolution of patient satisfaction throughout this process has not been evaluated. Here we performed a stratified analysis of patient-subjective cosmetic outcomes during the stages of breast reconstruction. Methods: Twenty-eight consecutive tissue expander-implant reconstructions were performed by the senior author using human acellular dermis. Cosmetic outcomes were assessed after each reconstructive stage using a validated Breast Evaluation Questionnaire consisting of questions related to breast size, shape and firmness in three separate contexts: intimate or sexual activities, leisure or social activities, and professional or job-related activities. Results: Eighteen patients underwent unilateral reconstruction, while 10 underwent bilateral reconstruction. Satisfaction scores were statistically higher following Stage I and II procedures for bilateral reconstructions. For unilateral reconstructions, there was a statistically significant elevation in scores following Stage II. The addition of nipple-areola reconstruction resulted in the highest scores for both unilateral and bilateral reconstructions. These score elevations were significant (p < 0.05) in nearly every measured context for unilateral reconstructions and as such, the significant differences in scores between unilateral and bilateral cohorts after stages I and II were nearly eliminated after completion of the entire reconstructive process. Conclusion: Satisfaction with tissue expander reconstruction is significantly affected by the patients' stage during the reconstructive process. Completion of all three stages, including nipple-areolar complex reconstruction, achieves maximal patient satisfaction. For unilateral reconstructions, completion of the entire reconstructive process, including contralateral symmetry procedures and nipple-areolar complex reconstruction, results in cosmesis scores that are similar to those in bilateral cases

Bone morphogenetic protein-9 effectively induces osteogenic differentiation of reversibly immortalized calvarial mesenchymal progenitor cells

AbstractCritical-sized craniofacial defect repair represents a significant challenge to reconstructive surgeons. Many strategies have been employed in an effort to achieve both a functionally and cosmetically acceptable outcome. Bone morphogenetic proteins (BMPs) provide a robust osteoinductive cue to stimulate bony growth and remodeling. Previous studies have suggested that the BMP-9 isoform is particularly effective in promoting osteogenic differentiation of mesenchymal progenitor cells. The aim of this study is to characterize the osteogenic capacity of BMP-9 on calvarial mesenchymal progenitor cell differentiation. Reversibly immortalized murine calvarial progenitor cells (iCALs) were infected with adenoviral vectors encoding BMP-9 or GFP and assessed for early and late stages of osteogenic differentiation in vitro and for osteogenic differentiation via in vivo stem cell implantation studies. Significant elevations in alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA transcription, osteopontin (OPN) protein expression, and matrix mineralization were detected in BMP-treated cells compared to control. Specifically, ALP activity was elevated on days 3, 7, 9, 11, and 13 post-infection and OCN mRNA expression was elevated on days 8, 10, and 14 in treated cells. Additionally, treatment groups demonstrated increased OPN protein expression on day 10 and matrix mineralization on day 14 post-infection relative to control groups. BMP-9 also facilitated the formation of new bone in vivo as detailed by gross, microcomputed tomography, and histological analyses. Therefore, we concluded that BMP-9 significantly stimulates osteogenic differentiation in iCALs, and should be considered an effective agent for calvarial tissue regeneration

Superficial Inferior Epigastric Artery Flap Salvage Technique Using Deep Inferior Epigastric Artery Graft

Summary:. Superficial inferior epigastric artery (SIEA) flap salvage remains challenging, particularly in cases of arterial insufficiency due to vessel spasm, pedicle kinking, or thrombosis. The already small, short SIEA pedicle, in addition to its inherent tendency toward spasm, renders the SIEA flap more difficult to manage when anastomotic revision is required. Furthermore, arterial thrombosis will cause dilation of the internal mammary artery, exacerbating vessel mismatch. In our previously published experience with 145 SIEA flaps, no flap with postoperative arterial thrombosis was salvageable. Following this experience, a new salvage technique using deep inferior epigastric artery grafts has been utilized and is described here

Video Capture of Plastic Surgery Procedures Using the GoPro HERO 3+

Background: Significant improvements can be made in recoding surgical procedures, particularly in capturing high-quality video recordings from the surgeons’ point of view. This study examined the utility of the GoPro HERO 3+ Black Edition camera for high-definition, point-of-view recordings of plastic and reconstructive surgery. Methods: The GoPro HERO 3+ Black Edition camera was head-mounted on the surgeon and oriented to the surgeon’s perspective using the GoPro App. The camera was used to record 4 cases: 2 fat graft procedures and 2 breast reconstructions. During cases 1-3, an assistant remotely controlled the GoPro via the GoPro App. For case 4 the GoPro was linked to a WiFi remote, and controlled by the surgeon. Results: Camera settings for case 1 were as follows: 1080p video resolution; 48 fps; Protune mode on; wide field of view; 16:9 aspect ratio. The lighting contrast due to the overhead lights resulted in limited washout of the video image. Camera settings were adjusted for cases 2-4 to a narrow field of view, which enabled the camera’s automatic white balance to better compensate for bright lights focused on the surgical field. Cases 2-4 captured video sufficient for teaching or presentation purposes. Conclusions: The GoPro HERO 3+ Black Edition camera enables high-quality, cost-effective video recording of plastic and reconstructive surgery procedures. When set to a narrow field of view and automatic white balance, the camera is able to sufficiently compensate for the contrasting light environment of the operating room and capture high-resolution, detailed video

A Simple, Safe Technique for Thorough Seroma Evacuation in the Outpatient Setting

Summary: Seroma formation, a common postoperative complication in reconstructive cases, can lead to capsular contracture and increased office visits and expenses. The authors present a safe, novel technique for ensuring the thorough removal of serous fluid in the outpatient setting. By relying on access with an angiocatheter, potential injury to permanent implants is minimized. The use of low continuous wall suction obviates the need of manual suction via multiple syringes and offers a rapid and thorough evacuation of all types of seromas

SSET Project: Cost-effectiveness Analysis of Surgical Specialty Emergency Trays in the Emergency Department

Background:. We hypothesize that reusable, on-site specialty instrument trays available to plastic surgery residents in the emergency department (ED) for bedside procedures are more cost-effective than disposable on-site and remote re-usable operating room (OR) instruments at our institution. Methods:. We completed a cost-effectiveness analysis comparing the use of disposable on-site kits and remote OR trays to a hypothetical, custom, reusable tray for ED procedures completed by PRS residents. Material costs of existing OR trays were used to estimate the purchasing and use-cost of a custom on-site tray for the same procedures. Cost of per procedure ‘consult time’ was estimated using procedure and resident salary. Results:. Sixteen bedside procedures were completed over a 4.5 month period. A mean of 2.14 disposable kits were used per-procedure. Mean consultation time was 1.66 hours. Procedures that used OR trays took 3 times as long as procedures that used on-site kits (4 vs. 1.1 hours). Necessary, additional instruments were unavailable for 75% of procedures. Mean cost of using disposable kits and OR trays was $115.03/procedure versus an estimated$26.67/procedure cost of using a custom tray, yielding $88.36/procedure cost-savings. Purchase of a single custom tray ($1,421.55) would be redeemed after 2.3 weeks at 1 procedure/day. Purchasing 4 trays has projected annual cost-savings of $26,565.20. Conclusion:. The purchase of specialized procedure trays will yield valuable time and cost-savings while providing quality patient care. Improving time efficiency will help achieve the Accreditation Council of Graduate Medical Education (ACGME) goals of maintaining resident well-being and developing quality improvement competency

Chyle Leak Management in the Setting of Tissue Expander Breast Reconstruction with Acellular Dermal Matrix: Case Series and Literature Review

Background:. Chylous leakage is a rare surgical complication most frequently encountered following operations involving the neck and thorax. Even more rare are axillary chyle leaks secondary to breast cancer involving the axillary lymph nodes. Anatomic variability in the termination of the thoracic duct may play a role in the susceptibility some individuals may have to this type of leakage. There is no consensus on the definitive management of these complications, especially in the context of breast reconstruction. Methods:. Here, we report our experience in the management of chylous leakage in three patients who underwent left axillary lymph node dissection and immediate breast reconstruction with the use of tissue expanders and acellular dermal matrix. Descriptions of each case are followed by a review of the relevant literature. We also present an original treatment algorithm. Results:. Two of three patients with suspected chylous leakage secondary to intraoperative injury to the axillary region underwent definitive diagnosis by clinical examination and drain fluid triglyceride analysis, followed by conservative management with a low-fat diet. The third patient was diagnosed clinically with no fluid analysis. All leakages resolved through conservative means, with no need to return to the operating room for surgical exploration and repair. Conclusions:. Based on our experience, we believe that patients with suspected chylous leakage secondary to axillary lymph node dissection in the context of breast reconstruction can be safely and effectively managed by conservative management in the acute postoperative period. If these measures are insufficient, surgical management may be necessary

Nationwide Bibliometric Analysis of Integrated Plastic Surgery Program Directors

Background:. Studies have linked bibliometric indices with the academic level of plastic surgeons, but this relationship has not been explored with residency program directors (PDs). As teachers of the next generation, PDs’ academic performance is an important component of residency program success. We sought to identify distinguishing characteristics of integrated plastic surgery programs, focusing on their PD bibliometric indices. Methods:. We identified plastic surgery programs based on 2021 Doximity reputation and research output rankings, respectively, and then divided them into four quartiles (Q1–Q4). PD academic history and bibliometric indices (h-index, the number of publications, and citations) were collected through Doximity profiles and program websites: PubMed, Scopus, Google Scholar, American Society of Plastic Surgeons, and Accreditation Council for Graduate Medical Education. Results:. Eighty-four programs were identified. There was a significant positive relationship between h-index, the number of publications, and type of research with reputation ranking (P < 0.05). After adjusting for years of experience post-training, h-index (OR = 1.24; P < 0.001) and the number of publications (OR = 1.05, P < 0.001) were significantly associated with reputation ranking. There was a statistically significant relationship between PD research fellowship completion and research output ranking (P < 0.01). After adjusting for years of experience post-training, h-index (OR = 1.05; P = 0.047) and the number of publications (OR = 1.01; P = 0.04) were significantly associated with research output ranking. Conclusion:. Higher ranked programs tend to have PDs who have a strong record of scholarly activity, as evidenced by certain bibliometric indices