Perivascular stem cells:a prospectively purified mesenchymal stem cell population for bone tissue engineering

Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone-forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence-activated cell sorting) of pericytes (CD146+CD34−CD45−) and adventitial cells (CD146−CD34+CD45−), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient-matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel-like molecule 1 (NELL-1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose-derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell-based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL-1 is a candidate growth factor able to induce human PSC osteogenesis

Leeching as salvage venous drainage in ear reconstruction: Clinical case and review of literature

Background: Ear avulsion is a rare complication of different traumas, such as car accidents, human or animal bites and stab wounds, and can result in dramatic cosmetic consequences for the patient. Ear replantation, revascularization, and reattachment are the options offering best aesthetic results. But venous outflow insufficiency is responsible for a high rate of failures. Leeching is one the most efficient methods to relieve venous congestion. It has been used as an alternative venous outflow in case of severe impairment of the physiologic one. Methods: We present a case of successful rescue of a congested reattached ear by leeching after subtotal avulsion, along with a review of the literature on cases of avulsed auricle reconstruction salvaged by hirudotherapy. Data were collected and analyzed to identify a best regimen to deal with venous congestion. Results: More than 130 cases of avulsed auricle savage are described in the literature, in a fourth of which leech therapy was used in the management of venous congestion. Discussion: In case of both venous outflow deficit or absence, leeches are a potentially successful option to correct the congestion while new veins reestablish normal physiology. The need for anticoagulant/antiaggregant therapy, antibiotics, and often blood transfusion are the main pitfalls of leeching. Conclusion: Leeches can be considered a salvage method for ear replantation and reattachment in those cases that lack venous outflow in the presence of valid arterial inflow

Preventing infective complications following leech therapy: Is practice keeping pace with current research?

Background: Despite several publications strongly advocating prophylactic antibiotics during leech therapy, and recent primary articles shedding new light on the microbiota of leeches, many units either do not use antibiotic prophylaxis, or are continuing to use ineffective agents. Methods: A 5-year follow-up of plastic surgery units in the United Kingdom and the Republic of Ireland was conducted in 2007 to ascertain current practice regarding the use of prophylactic antibiotics with leech therapy. A comprehensive literature search investigated primary research articles regarding the microbiota of leeches to update the reconstructive surgery community. Results: Despite published evidence to support the use of prophylactic antibiotics during leech therapy, 24% of units do not use antibiotic prophylaxis and 57% of those using antibiotics are using potentially ineffective agents. Advanced molecular genetic techniques, which allow accurate characterization of both culturable and nonculturable microbiota of the leech digestive tract, show a wider diversity than at first thought, with variable antiobiotic resistance profiles. Conclusions: Despite infection due to leech therapy being a well known and relatively common complication, many units are not using appropriate antibiotic prophylaxis. © 2009 Wiley-Liss, Inc. Microsurgery 2009

Autologous microsurgical breast reconstruction and coronary artery bypass grafting: an anatomical study and clinical implications

OBJECTIVE: To identify possible avenues of sparing the internal mammary artery (IMA) for coronary artery bypass grafting (CABG) in women undergoing autologous breast reconstruction with deep inferior epigastric artery perforator (DIEP) flaps. BACKGROUND: Optimal autologous reconstruction of the breast and coronary artery bypass grafting (CABG) are often mutually exclusive as they both require utilisation of the IMA as the preferred arterial conduit. Given the prevalence of both breast cancer and coronary artery disease, this is an important issue for women's health as women with DIEP flap reconstructions and women at increased risk of developing coronary artery disease are potentially restricted from receiving this reconstructive option should the other condition arise. METHODS: The largest clinical and cadaveric anatomical study (n=315) to date was performed, investigating four solutions to this predicament by correlating the precise requirements of breast reconstruction and CABG against the anatomical features of the in situ IMAs. This information was supplemented by a thorough literature review. RESULTS: Minimum lengths of the left and right IMA needed for grafting to the left-anterior descending artery are 160.08 and 177.80 mm, respectively. Based on anatomical findings, the suitable options for anastomosis to each intercostals space are offered. In addition, 87-91% of patients have IMA perforator vessels to which DIEP flaps can be anastomosed in the first- and second-intercostal spaces. CONCLUSION: We outline five methods of preserving the IMA for future CABG: (1) lowering the level of DIEP flaps to the fourth- and fifth-intercostals spaces, (2) using the DIEP pedicle as an intermediary for CABG, (3) using IMA perforators to spare the IMA proper, (4) using and end-to-side anastomosis between the DIEP pedicle and IMA and (5) anastomosis of DIEP flaps using retrograde flow from the distal IMA. With careful patient selection, we hypothesize using the IMA for autologous breast reconstruction need not be an absolute contraindication for future CABG

Titanium cranioplasty in children and adolescents

Full thickness calvarial defects present considerable challenges to reconstructive surgeons. In paediatric cases, the use of biomaterials as a substrate for cranioplasty rather than autologous bone is controversial. Alloplastic cranioplasty in adults is supported by several large case series however long term outcome of biomaterial use in paediatric cases is limited. Retrospective seven year analysis of departmental database and clinical records identified 22 patients aged under 18 who had undergone 23 custom made titanium cranioplasties by a single surgeon using the same technique. Data including patient demographics, reason for craniectomy and complications experienced following surgery was obtained. The mean age at operation was 12 years 9 months. The mean defect size was 44.3cm2. No significant complications related to the cranioplasty were recorded in the early post operative period or during long term review (average follow up 4 years 6 months). No cranioplasty implant required removal. This retrospective case series shows that custom made patient specific titanium cranioplasty is a viable alternative to autologous bone as a reconstructive material in paediatric patients under specific circumstances

Relative contributions of adipose-resident CD146 pericytes and CD34 adventitial progenitor cells in bone tissue engineering

Bone repair: synergistic healing from two types of fat cells Different kinds of cells found surrounding blood vessels in fat play a complementary and synergistic role in bone healing. Aaron James from Johns Hopkins University in Baltimore, MD, USA, and colleagues derived two subsets of cells from human fat tissue: contractile cells known as pericytes that wrap around cellular lining of capillaries and tiny veins; and connective tissue cells known as adventitial cells that surrounds larger vessels. Under isolated culture conditions, pericytes stimulated the development of primitive blood vessels, whereas adventitial cells promoted early bone formation. The researchers applied the cells to the sites of bone defects in mice and saw that combined treatment with both pericytes and adventitial cells led to greater bone repair than treatment with either cell type alone