Stephen M Warren

Duke University Medical Center, Durham, North Carolina, United States

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Publications (160)428.73 Total impact

  • Raj M Vyas, Stephen M Warren
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    ABSTRACT: Modern cleft surgery requires four-dimensional and functional anatomic understanding of the cleft (and noncleft) lip, nose, and alveolus. Some techniques for nasolabial repair rely more on precise anatomic geometry, whereas others afford the surgeon a more flexible design. Consistent anthropometry enables accurate assessment and reporting of long-term outcomes; such reports are needed to guide perioperative care, delineate optimal repair principles, and resolve ongoing controversies.
    Clinics in plastic surgery 04/2014; 41(2):165-177. · 0.95 Impact Factor
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    ABSTRACT: Non-healing foot ulcers are the most common cause of non-traumatic amputation and hospitalization amongst diabetics in the developed world. Impaired wound neovascularization perpetuates a cycle of dysfunctional tissue repair and regeneration. Evidence implicates defective mobilization of marrow-derived progenitor cells (PCs) as a fundamental cause of impaired diabetic neovascularization. Currently, there are no FDA-approved therapies to address this defect. Here we report an endogenous PC strategy to improve diabetic wound neovascularization and closure through a combination therapy of AMD3100, which mobilizes marrow-derived PCs by competitively binding to the cell surface CXCR4 receptor, and PDGF-BB, which is a protein known to enhance cell growth, progenitor cell migration and angiogenesis. Wounded mice were assigned to 1 of 5 experimental arms (n = 8/arm): saline treated wild-type, saline treated diabetic, AMD3100 treated diabetic, PDGF-BB treated diabetic, and AMD3100/PDGF-BB treated diabetic. Circulating PC number and wound vascularity were analyzed for each group (n = 8/group). Cellular function was assessed in the presence of AMD3100. Using a validated preclinical model of type II diabetic wound healing, we show that AMD3100 therapy (10 mg/kg; i.p. daily) alone can rescue diabetes-specific defects in PC mobilization, but cannot restore normal wound neovascularization. Through further investigation, we demonstrate an acquired trafficking-defect within AMD3100-treated diabetic PCs that can be rescued by PDGF-BB (2 μg; topical) supplementation within the wound environment. Finally, we determine that combination therapy restores diabetic wound neovascularization and accelerates time to wound closure by 40%. Combination AMD3100 and PDGF-BB therapy synergistically improves BM PC mobilization and trafficking, resulting in significantly improved diabetic wound closure and neovascularization. The success of this endogenous, cell-based strategy to improve diabetic wound healing using FDA-approved therapies is inherently translatable.
    PLoS ONE 01/2014; 9(3):e92667. · 3.73 Impact Factor
  • Parit A Patel, Stephen M Warren, Joseph G McCarthy
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    ABSTRACT: Maxillary mucoceles are a relatively rare entity especially following surgical procedures involving osteotomies of the maxilla. The etiology of maxillary mucoceles has been ascribed to facial trauma (fractures), sinus surgery, and chronic inflammatory diseases or infections. Mucoceles can follow injury to the sinus mucosa and/or sinus outflow tract with a resulting expansile cystic mass. The clinical presentation ranges from swelling, pain, a palpable mass, proptosis, enophthalmos, and diplopia. The treatment involves either open or endoscopic incision and drainage of the cyst, mucosal resection, and an antrostomy for drainage.We report the case of a patient with Pfeiffer syndrome who underwent Le Fort III distraction osteogenesis and developed a symptomatic mucocele 15 years postoperatively.
    The Journal of craniofacial surgery 11/2013; 24(6):2000-2. · 0.81 Impact Factor
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    ABSTRACT: Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 × 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 09/2013; · 4.43 Impact Factor
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    ABSTRACT: The mechanotransduction mechanisms linking distraction device activation to new bone formation remain unknown. We hypothesize that the tension stress of activation during distraction osteogenesis is transmitted through lacunocanalicular fluid flow to initiate the osteogenic signaling cascade. Adult Sprague-Dawley rats (N = 24) were subjected to mandibular osteotomy and application of an external distraction device. After a 3-day latency period, half the animals (n = 12) underwent device activation at 0.25 mm twice daily for 6 days (total activation, 3 mm), and the other half (n = 12) had no activation. On day 10, the animals were injected with fluorescent reactive red lacunocanalicular tracer before killing. Mandibles were harvested, embedded, and sectioned, and reactive red epifluorescence lacunocanalicular flow was measured. Protein was harvested for focal adhesion kinase 1 (FAK1), NESPRIN1, SUN1, LAMIN A/C, and SMAD1 Western blotting as well as for bone morphogenetic protein (BMP)-2 enzyme-linked immunosorbent assay and alkaline phosphatase assay. Lacunocanalicular fluid flow was significantly greater in the distracted samples (60.5 ± 14 vs 10.3 ± 4 molecules of equivalent soluble fluorochrome per megapixel, P = 0.01). Flow distribution demonstrated the highest lacunocanalicular flow near the center of the distraction gap. Increased lacunocanalicular flow resulted in increased FAK1 (P = 0.009), NESPRIN1 (P = 0.01), SUN1 (P = 0.01), and LAMIN A/C (P = 0.008) expression. Focal adhesion kinase 1 activation in the presence of BMP-2 protein expression (P = 0.001) resulted in increased intranuclear SMAD1 phosphorylation (P = 0.04) and alkaline phosphatase activity (P < 0.0001). These findings suggest that activation of the distraction osteogenesis device affects cellular response through changes in lacunocanalicular fluid flow.
    The Journal of craniofacial surgery 09/2013; 24(5):1558-64. · 0.81 Impact Factor
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    ABSTRACT: Delayed diabetic (DM) wound healing is, in part, the result of inadequate endothelial progenitor cell (EPC) proliferation, mobilization, and trafficking. Recently, we developed a serum free functional culture system called quantity and quality control culture system (QQc) which enhances the number and vasculogenic potential of EPCs. We hypothesize that QQc restoration of DM EPC function will improve wound closure. In order to test this hypothesis, we measured pre/post-QQc DM KSL (e.g. c-kit(+)Sca-1(+)lin(-)) cell activity in vitro as well as the effect of KSL cell adoptive transfer on the rate of euglycemic wound closure. KSL cells were magnetically sorted from control and streptozotocin-induced Type I DM C57BL6J bone marrow. Freshly isolated control and DM KSL cells were cultured in QQc for 7 days and pre/post-QQc KSL function was tested. The number of KSLs significantly increased post QQc for both DM and controls and also increasing DM -KSL vasculogenic potential above fresh control KSL level. Similarly, fresh DM cells form fewer tubules, but QQc increases DM tubule formation to greater than fresh control cell levels (p<0.05). Adoptive transfer of post-QQc DM KSL cells significantly enhance wound closure compared to fresh DM KSL cells and equaled wound closure of post-QQc control KSL cells. Post-QQc DM KSL enhancement of wound closure is mediated, in part, via a vasculogenic mechanism. This study demonstrates that QQc can reverse DM EPC dysfunction and achieve control-levels of EPC function. Finally, post-QQc DM EPC therapy effectively improved euglycemic wound closure and may improve DM wound healing.
    Diabetes 05/2013; · 7.90 Impact Factor
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    ABSTRACT: Nonhealing bone defects are difficult to treat. As the bone morphogenic protein and transforming growth factor beta pathways have been implicated in bone healing, we hypothesized that percutaneous Smad7 silencing would enhance signaling through both pathways and improve bone formation. Critical sized parietal trephine defects were created and animals received percutaneous injection of: agarose alone or agarose containing nonsense or Smad7 small interfering RNA (siRNA). At 12 weeks, SMADs1, 2, 3, 5, 7 and 8 levels were assessed. Smad1/5/8 osteogenic target, Dlx5, and SMAD2/3 angiogenic target, plasminogen activator inhibitor-1 (Pai1), transcription levels were measured. Noncanonical signaling through TGFβ activated kinase-1 (Tak1) and target, runt-related transcription factor 2 (Runx2) and collagen1α1 (Col1α1), transcription were also measured. Micro-computed tomography and Gomori trichome staining were used to assess healing. Percutaneous injection of Smad7 siRNA significantly knocked down Smad7 mRNA (86.3±2.5%) and protein levels (46.3±3.1%). The SMAD7 knockdown resulted in a significant increase in receptor-regulated SMADs (R-SMAD) (Smad 1/5/8 and Smad2/3) nuclear translocation. R-SMAD nuclear translocation increased Dlx5 and Pai1 transcription. Additionally, noncanonical signaling through Tak1 increased Runx2 and Col1α1 target transcription. Compared with animals treated with agarose alone (33.9±2.8% healing) and nonsense siRNA (31.5±11.8% healing), animals treated Smad7 siRNA had significantly great (91.2±3.8%) healing. Percutaneous Smad7 silencing increases signal transduction through canonical and noncanonical pathways resulting in significant bone formation. Minimally invasive gene therapies may prove effective in the treatment of nonhealing bone defects.Gene Therapy advance online publication, 18 April 2013; doi:10.1038/gt.2013.15.
    Gene therapy 04/2013; · 4.75 Impact Factor
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    ABSTRACT: Since bone repair and regeneration depend on vasculogenesis and osteogenesis, both of these processes are essential for successful vascularized bone engineering. Using adipose-derived stem cells (ASCs), we investigated temporal gene expression profiles, as well as bone nodule and endothelial tubule formation capacities, during osteogenic and vasculogenic ASC lineage commitment. Osteoprogenitor-enriched cell (OPEC) populations were found to express RUNX2, MSX2, SP7 (osterix), BGLAP (osteocalcin), SPARC (osteonectin), and SPP1 (osteopontin) in a temporally specific sequence. Irreversible commitment of ASCs to the osteogenic lineage occurred between days 6 and 9 of differentiation. Endothelioprogenitor-enriched cell (EPEC) populations expressed CD34, PECAM1 (CD31), ENG (CD105), FLT1 (VEGFR1), and KDR (VEGFR2). Capacity for microtubule formation was evident in as early as 3 days. Functional capacity was assessed in eight co-culture combinations for both bone nodule and endothelial tubule formation, and the greatest expression of these end-differentiation phenotypes was observed in the combination of well-differentiated endothelial cells with less-differentiated osteoblastic cells. Taken together, our results demonstrate vascularized bone engineering utilizing ASCs is a promising enterprise, and that co-culture strategies should focus on developing a more mature vascular network in combination with a less mature osteoblastic stromal cell.
    Tissue Engineering Part A 01/2013; · 4.64 Impact Factor
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    ABSTRACT: The incidence of postoperative complications in cleft care is low. In this 19-year retrospective analysis of cleft lip and palate patients treated with preoperative nasoalveolar molding, we examine the incidence of postoperative oronasal fistulae. The charts of 178 patients who underwent preoperative nasoalveolar molding by the same orthodontist/prosthodontist team and primary cleft lip/palate repair by the same surgeon over a 19-year period were reviewed. Millard, Mohler, Cutting, or Mulliken-type techniques were used for cleft lip repairs. Oxford-, Bardach-, or von Langenbeck-type techniques were used for cleft palate repairs. One nasolabial fistula occurred after primary cleft lip repair (0.56% incidence) and was repaired surgically. Four palatal fistulae (3 at the junction between soft and hard palate and 1 at the right anterior palate near the incisive foramen) occurred, but 3 healed spontaneously. Only 1 palatal fistula (0.71%) required surgical repair. All 5 fistulae occurred within the first 8 years of the study period, with 4 (80%) of 5 occurring within the first 3 years. Although fistula rate may be related to surgeon experience and the evolution of presurgical techniques, nasoalveolar molding in conjunction with nasal floor closure contributes to a low incidence of oronasal fistulae.
    The Journal of craniofacial surgery 01/2013; 24(1):57-61. · 0.81 Impact Factor
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    ABSTRACT: Despite significant advances in cleft lip and palate treatment, anatomical controversies remain. Some have proposed that the width of the cleft is due to alveolar segmental displacement. Others suggest that the width is due to palatoalveolar hypoplasia. Improving our understanding of cleft anatomy may have implications for presurgical orthopedics and tissue engineering therapies. Palatoalveolar impressions of 17 noncleft children and 11 children with complete (alveolar, primary, and secondary) unilateral cleft palates were taken. Maxillary tuberosity positions and maxillary volumes were compared. Tuberosity position was determined by facebow transfer of palatoalveolar casts into geodetic datum boxes, and identification of the Cartesian coordinates (x, y, z) of the tuberosities relative to the box surfaces and Frankfurt horizontal. Maxillary volume was determined by immersing the palatoalveolar casts and measuring sand displacement. A significant difference was noted in the average tuberosity to contralateral tuberosity distance between cleft and noncleft cohorts. On average, cleft palate tuberosities were laterally displaced 8.7 mm compared with noncleft palates (P < 0.05). There was neither statistically significant alveolar segment elevation nor retroversion. A significant difference was noted in the average palatoalveolar volumes. The cleft palatoalveolar volume was 5.7 cm, and the noncleft palatoalveolar volume was 7.2 cm (P < 0.05). A palatal cleft is due to both alveolar tissue displacement and deficiency. Therefore, ideal cleft palate care should involve the correction of a displaced and deficient alveolus.
    The Journal of craniofacial surgery 01/2013; 24(1):89-93. · 0.81 Impact Factor
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    ABSTRACT: Preoperative nasoalveolar molding (NAM) in combination with primary gingivoperiosteoplasty (GPP) reduces the need for secondary alveolar bone grafting by 60% in patients with unilateral cleft lip and palate (CL/P). Herein, we investigate the efficacy of NAM and primary GPP in patients with bilateral CL/P. All patients (n = 38) with bilateral CL/P who underwent NAM and primary GPP from 1988 to 1998 with at least 14 years of follow-up were included in this study. Panoramic and periapical radiographs were used to assess dentoalveolar bone formation. A total of 38 patients were identified with median follow-up of 18 years (range 14-26 years). Of the 27 patients who underwent bilateral GPP, 14 (51%) patients had successful dentoalveolar bone formation bilaterally and 13 (49%) had unilateral bone formation. No patient had a bilateral failure. Of the 11 patients who underwent unilateral GPP, 7 (63%) patients had successful dentoalveolar bone formation. Bilateral successful dentoalveolar bone formation following primary bilateral GPP has a dependent probability of 52% and a conditional probability of 82%.
    The Journal of craniofacial surgery 01/2013; 24(1):186-90. · 0.81 Impact Factor
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    ABSTRACT: Among the craniosynostosis syndromes, Pfeiffer syndrome is notable because of high mortality and the need for multiple surgical interventions. However, it is variable in severity. We propose a new classification of Pfeiffer Syndrome to define pathology and function. A retrospective review was conducted of 42 patients with Pfeiffer syndrome treated from 1975 to 2010, the largest series reported to date. The classification was based on a functional assessment of patients in terms of respiratory, ocular, otological, and neurological status. This classification was tested by scoring and stratifying patients as follows: type A (mild problems), B (moderate problems), or C (severe problems). Patients were scored both at the time of presentation and after all surgical interventions to assess change in functional outcome. The functional classification system was compared to another previously reported. Type A patients did not have any change in postoperative functional outcomes (mean preoperative score 1.6, mean postoperative score 1.6); type B patients showed functional improvement (mean preoperative score 4.1, mean postoperative score 3.4) but type C patients (mean preoperative score 7.7, mean postoperative score 4.8) demonstrated the greatest improvement in functional scores after surgical intervention. Suture pathology did not indicate the clinical severity of phenotype, a variance from a previously published classification. The proposed classification is useful to assess severity of phenotype: respiratory, ocular, otologic, and neurologic problems are key indicators of the need for treatment. The classification can provide a helpful guide in multidisciplinary treatment planning, in reporting outcomes, and in the sharing of data among craniofacial anomalies centers.
    The Journal of craniofacial surgery 01/2013; 24(1):204-15. · 0.81 Impact Factor
  • Court B Cutting, Stephen M Warren
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    ABSTRACT: Nearly 60 years ago, Joseph Murray described several advancements to Bradford Cannon's Abbe flap reconstruction of secondary bilateral cleft lips in order to simplify the technique and improve results. Unlike their predecessors, Drs. Cannon and Murray modified the Abbe flap by splitting its apex in order to obtain a symmetrical correction of the upper lip and allow the 2 suture lines to extend vertically and laterally past the base of the columella and disappear within the floor of the nose. Eighteen years later, Dr. Murray reviewed the evolution of his own secondary cleft lip reconstruction experience to include a new approach to advance the maxilla rather than set back the mandible. In this Signature Issue, we reflect on contemporary innovations in secondary bilateral cleft lip Abbe flap reconstruction. Today, we approach the secondary reconstruction of the bilateral cleft lip in 3 stages. First, we establish normal anatomic positioning of the midface. Second, we perform secondary cleft nasal surgery as necessary. Finally, only after the midfacial skeleton and nose have been treated do we proceed with Abbe flap reconstruction of the upper lip. We inset the Abbe flap a quarter of the way out on the columella and wrap the Abbe darts around the sides of the columella. We find that designing the Abbe flap this way avoids the saber cut-like notching at the lip-columella junction, redundant vermilion, and excess flap length, and it also reduces or eliminates the need for upper or lower lip scar revision.
    The Journal of craniofacial surgery 01/2013; 24(1):75-8. · 0.81 Impact Factor
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    ABSTRACT: : The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24) mouse could serve as a model of senescent wound healing. : Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24 mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry. : Zmpste24 mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24 wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial. : The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24 progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.
    Plastic and reconstructive surgery 12/2012; 130(6):788e-98e. · 2.74 Impact Factor
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    ABSTRACT: Bone repair and regeneration are dynamic processes that involve a complex interplay between the substrate, local and systemic cells, and the milieu. Although each constituent plays an integral role in faithfully recreating the skeleton, investigators have long focused their efforts on scaffold materials and design, cytokine and hormone administration, and cell-based therapies. Only recently have the intangible aspects of the milieu received their due attention. In this review, we highlight the important influence of environmental factors on bone tissue engineering. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 11/2012; · 2.31 Impact Factor
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    ABSTRACT: Impaired wound healing remains a major clinical problem with many etiologies. Altering gene expression to enhance healing is an innovative therapeutic approach. In recent years, we have developed a means to topically silence genes at the post-transcriptional level to locally alter wounds and improve the healing process. Many types of chronic wounds have been associated with alterations in the expression of genes that mediate healing. Targeting the expression of these genes in a way that can improve healing while limiting systemic side effects has been very challenging. Our laboratory's recent work has focused on the use of topically applied small interfering ribonucleic acid (siRNA) to inhibit messenger RNA expression of certain mediators involved in healing in two different types of cutaneous injury-radiation-induced cutaneous injury and the diabetic excisional wound. By successfully inhibiting specific gene mediators with topical siRNA, we reversed downstream signaling pathways, which led to expedited wound healing in diabetic wounds and restoration to a more normal phenotype in radiation-induced skin injuries. The signaling pathways and gene mediators that we targeted and inhibited in murine models are present in humans. Applying parallel treatment strategies in humans may provide novel means of treating these burdensome and costly conditions. Our novel method for local gene silencing is effective in treating various types of cutaneous murine wounds. Topical gene silencing with siRNA obviates the side effects of systemic medication and has the potential to be effective in healing or preventing a wide array of cutaneous human conditions.
    Advances in wound care. 10/2012; 1(5):218-223.
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    ABSTRACT: A serious consequence of diabetes mellitus is impaired wound healing, which largely resists treatment. We previously reported that topical application of calreticulin (CRT), an endoplasmic reticulum chaperone protein, markedly enhanced the rate and quality of wound healing in an experimental porcine model of cutaneous repair. Consistent with these in vivo effects, in vitro CRT induced the migration and proliferation of normal human cells critical to the wound healing process. These functions are particularly deficient in poor healing diabetic wounds. Using a genetically engineered diabetic mouse (db/db) in a full-thickness excisional wound healing model, we now show that topical application of CRT induces a statistically significant decrease in the time to complete wound closure compared with untreated wounds by 5.6 days (17.6 vs. 23.2). Quantitative analysis of the wounds shows that CRT increases the rate of reepithelialization at days 7 and 10 and increases the amount of granulation tissue at day 7 persisting to day 14. Furthermore, CRT treatment induces the regrowth of pigmented hair follicles observed on day 28. In vitro, fibroblasts isolated from diabetic compared with wild-type mouse skin and human fibroblasts cultured under hyperglycemic compared with normal glucose conditions proliferate and strongly migrate in response to CRT compared with untreated controls. The in vitro effects of CRT on these functions are consistent with CRT's potent effects on wound healing in the diabetic mouse. These studies implicate CRT as a potential powerful topical therapeutic agent for the treatment of diabetic and other chronic wounds.
    Wound Repair and Regeneration 09/2012; 20(5):715-30. · 2.76 Impact Factor
  • Katie E Weichman, Stephen M Warren
    The Journal of craniofacial surgery 07/2012; 23(4):1019. · 0.81 Impact Factor
  • Jordan Jacobs, Stephen M Warren
    The Journal of craniofacial surgery 07/2012; 23(4):1220-1. · 0.81 Impact Factor
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    ABSTRACT: Since obesity impairs wound healing and bone marrow (BM)-derived vasculogenic progenitor cells (PCs) are important for tissue repair, we hypothesize that obesity-impaired wound healing is due, in part, to impaired PC mobilization, trafficking, and function. Peripheral blood was obtained from nondiabetic, obese (BMI > 30, n = 25), and nonobese (BMI < 30, n = 17) subjects. Peripheral blood human (h)PCs were isolated, quantified, and functionally assessed. To corroborate the human experiments, 6-mm stented wounds were created on nondiabetic obese mice (TALLYHO/JngJ, n = 15) and nonobese mice (SWR/J, n = 15). Peripheral blood mouse (m)PCs were quantified and wounds were analyzed. There was no difference in the number of baseline circulating hPCs in nondiabetic, obese (hPC-ob), and nonobese (hPC-nl) subjects, but hPC-ob had impaired adhesion (p < 0.05), migration (p < 0.01), and proliferation (p < 0.001). Nondiabetic obese mice had a significant decrease in the number of circulating PCs (mPC-ob) at 7 (p = 0.008) and 14 days (p = 0.003) after wounding. The impaired circulating mPC-ob response correlated with significantly impaired wound closure at days 14 (p < 0.001) and 21 (p < 0.001) as well as significantly fewer new blood vessels in the wounds (p < 0.001). Our results suggest that obesity impairs the BM-derived vasculogenic PC response to peripheral injury and this, in turn, impairs wound closure.
    Wound Repair and Regeneration 06/2012; 20(4):512-22. · 2.76 Impact Factor

Publication Stats

2k Citations
428.73 Total Impact Points

Institutions

  • 2013
    • Duke University Medical Center
      Durham, North Carolina, United States
  • 2011–2013
    • NYU Langone Medical Center
      • Department of Plastic Surgery
      New York City, NY, United States
  • 2008–2013
    • American Society of Ophthalmic Plastic and Reconstructive Surgery
      New York City, New York, United States
    • Boston Children's Hospital
      Boston, Massachusetts, United States
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 2002–2013
    • State University of New York Downstate Medical Center
      • • Division of Plastic Surgery
      • • Department of Surgery
      Brooklyn, NY, United States
  • 2012
    • University of Pittsburgh
      • Department of Epidemiology
      Pittsburgh, PA, United States
    • Temple University
      • Department of Surgery
      Philadelphia, PA, United States
    • University of California, San Francisco
      • Division of Craniofacial Anomalies
      San Francisco, CA, United States
  • 2002–2012
    • Stanford University
      • • Department of Surgery
      • • Division of Plastic and Reconstructive Surgery
      Stanford, CA, United States
  • 2007–2010
    • CUNY Graduate Center
      New York City, New York, United States
    • New York University
      • Institute of Reconstructive Plastic Surgery
      New York City, NY, United States
    • Weill Cornell Medical College
      New York City, New York, United States
  • 2005
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 2002–2005
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Division of Plastic Surgery
      Boston, MA, United States
  • 2004
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2002–2004
    • Stanford Medicine
      • Department of Surgery
      Stanford, California, United States