Lauren Kokai - Academia.edu (original) (raw)
Papers by Lauren Kokai
Plastic & Reconstructive Surgery
Plastic and Aesthetic Research
Autologous fat grafting is an important surgical technique in aesthetic and reconstructive proced... more Autologous fat grafting is an important surgical technique in aesthetic and reconstructive procedures. Fat grafting for breast reconstruction is now an established procedure for adding volume and improving cutaneous pliability; it can be used independently to replace more invasive flap procedures or implants, or as an adjunct for smaller volume supplementation. The breadth of applications in the breast necessitates diversity in technique and approach, and while there is no universally agreed-upon protocol, basic principles have guided the evolution of some commonly adopted tenets. Broadly, fat grafting outcomes are highly favorable but dependent on patient and procedure factors, requiring learned patient selection and expertise in recipient site assessment. Common complications from fat grafting, such as fat necrosis and the development of nodules, are particularly troublesome for post-oncologic patients, requiring considerable pre-surgical consultation for patient education and man...
Aesthetic Surgery Journal
Background Autologous fat grafting, although broadly indicated, is limited by unsatisfactory rete... more Background Autologous fat grafting, although broadly indicated, is limited by unsatisfactory retention and often requires multiple procedures to achieve durable outcomes. Graft survival is strongly influenced by the magnitude and duration of post-engraftment ischemia. Calcitriol is a pleiotropic, safe nutrient with cell-specific influence on viability and metabolic flux. Objectives Evaluate the efficacy of activated vitamin D3 (calcitriol) in improving grafting outcomes and examine its mechanisms. Methods Lipoaspirate was collected for ex vivo culture (7 unique donors), in vitro bioenergetic analysis (6 unique donors), and in vivo transplantation (5 unique donors). Ex vivo samples were incubated for up to 2 weeks before extraction of the stromal vascular fraction (SVF) for viability or flow cytometry. SVF was collected for Seahorse (Agilent; Santa Clara, CA) analysis of metabolic activity. Human endothelial cell lines were utilized for analyses of endothelial function. In vivo, samp...
Facial Plastic Surgery & Aesthetic Medicine
Stem Cells and Development
Adipose therapeutics, including isolated cell fractions and tissue emulsifications, have been exp... more Adipose therapeutics, including isolated cell fractions and tissue emulsifications, have been explored for osteoarthritis (OA) treatment, however the optimal preparation method and bioactive tissue component for healing has yet to be determined. This in-vitro study compared the effects of adipose preparations on cultured knee chondrocytes. De-identified human articular chondrocytes were co-cultured with adipose preparations for 36 or 72 hours. Human adipose tissues were obtained from abdominal panniculectomy procedures and processed using three different techniques: enzymatic digestion to release stromal vascular fraction (SVF), emulsification with luer-to-luer transfer (nanofat), and processing in a bead-mill (Lipogems, Lipogems International SpA, Milan, Italy). Gene expression in both chondrocytes and adipose preparations was measured to assess cellular inflammation, catabolism, and anabolism. Results demonstrated that chondrocytes cultured with SVF consistently showed increased inflammatory and catabolic gene expression compared to control chondrocytes at both 36-and 72-hour timepoints. Alternatively, chondrocytes co-cultured with either nanofat or bead-mill processed adipose derivatives yielded minimal pro-inflammatory effects and instead increased anabolism and regeneration of cartilage extracellular matrix. Interestingly, nanofat preparations induced transient matrix anabolism while Lipogems adipose consistently demonstrated increased matrix synthesis at both study time points following co-culture. This evaluation of the regenerative potential of adipose-derived preparations as a clinical tool for knee OA treatment suggests that mechanically processed preparations may be more efficacious than an isolated SVF cell preparation.
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Journal of Burn Care & Research, Mar 23, 2022
Introduction: Adipose and adipose-derived stem cell therapies have met success as adjunctive trea... more Introduction: Adipose and adipose-derived stem cell therapies have met success as adjunctive treatment during burn reconstruction with well described benefit in the delayed-treatment of soft-tissue deficits. While the use of allogeneic skin is well-described, adipose tissues have typically remained autologous. Allogenic fat is not commonly used in burn care, however, in large, complex burns where autologous tissue is limited adipose may not be readily available for harvest or use. Understanding the efficacy of allogeneic tissues in this setting is critical to expand our reconstructive options. Here we describe a protocol utilizing allogeneic fat as well as examine the efficacy of this approach on burn-wound contractures, adhesions, and soft-tissue deficits. Methods: Female, Yorkshire swine received 16, 4x4 cm full-thickness burns. After 48 hours, eschar was removed to fascia. Wounds were stratified to receive either A) No Reconstruction, B) Skin-Only, C) Fat-Only, D) Immediate-Skin, Delayed-Fat, or E) Immediate-Fat, Delayed-Skin. All fat utilized was allogeneic sourced from vendor-matched swine. At 8-weeks post-engraftment animals were sacrificed and all wounds were collected for photography, ultrasound, histology and serum studies. Results: Use of allogeneic fat significantly improved terminal soft-tissue thickness under both immediate and delayed administration (p< 0.05). Immediate use of allogeneic fat significantly improved tissue mobility vs. untreated and skin graft controls (p< 0.05). Contracture was most significantly affected by timing of skin graft placement, however, could be further mitigated under standard delayed-fat approached with allogeneic tissue. Conclusions: Here we demonstrate use of allogeneic fat in both traditional-delayed and a fat-first approach with significant mitigation of adhesion when applied as an initial basal layer. Both immediate and delayed allogeneic fat were sufficient to improve on soft tissue deficits.
Plastic and Reconstructive Surgery - Global Open, 2022
Plastic and Reconstructive Surgery Global Open, 2017
METHODS: Collagenase derived from Clostridium Histolyticum was used in a randomized, double-blind... more METHODS: Collagenase derived from Clostridium Histolyticum was used in a randomized, double-blinded, placebo controlled study on a total of 19 healthy subjects, each with two biopsy-proven lipomas of similar size (one to receive drug and one to receive placebo) at two independent investigational centers (Office of Z. Gerut and Dept. of Plastic Surgery Vanderbilt Univ. Med Ctr.). An independent pharmacist prepared the research drug and the placebo for injection and the two indiscernible preparations were randomized for injection into the two lipomas of each subject; all staff including the investigators, as well as the subject were blinded.
Acta Pharmaceutica Sinica B, 2021
PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute l... more PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury. Mice received 1500 U/kg of PEG-ASNase and were sacrificed 1, 3, 5, and 7 days after drug administration. Liver triglycerides were quantified, and plasma bilirubin, ALT, AST, and non-esterified fatty acids (NEFA) were measured. The mRNA and protein levels of genes involved in hepatic fatty acid synthesis, β-oxidation, very low-density lipoprotein (VLDL) secretion, and white adipose tissue (WAT) lipolysis were determined. Mice developed hepatic steatosis after PEG-ASNase, which associated with increases in bilirubin, ALT, and AST. The hepatic genes Ppara, Lcad/Mcad, Hadhb, Apob100, and Mttp were upregulated, and Srebp-1c and Fas were downregulated after PEG-ASNase. Increased plasma NEFA, WAT loss, and adipose tissue lipolysis were also observed after PEG-ASNase. Furthermore, we found that PEG-ASNase-induced liver injury was exacerbated in obese and aged mice, consistent with clinical studies of ASNase-induced liver injury. Our data suggest that PEG-ASNase-induced liver injury is due to drug-induced lipolysis and lipid redistribution to the liver.
19. Chiaki Komatsu, Yolandi van der Merwe, Lin He, Maxine R. Miller, Katie A. Lucy, Huamin Tang, ... more 19. Chiaki Komatsu, Yolandi van der Merwe, Lin He, Maxine R. Miller, Katie A. Lucy, Huamin Tang, Ian Rosner, Wendy Chen, Jila Noori, Valeria Fu, Michael Steketee, Gadi Wollstein, Mario Solari, Joel S. Schuman, Kevin C. Chan, Kia M. Washington. Retinal and optic nerve viability evaluated with optical coherence tomography, manganese-enhanced MRI and electroretinography after whole eye transplantation
INTRODUCTION Tissue engineered vascular grafts (TEVGs) seeded with autologous cells offer a treat... more INTRODUCTION Tissue engineered vascular grafts (TEVGs) seeded with autologous cells offer a treatment alternative to current coronary artery by-pass procedures1-4. Past work has demonstrated that TEVGs seeded with only a mesenchymal stem cell (MSC) population will remodel in vivo5. However, the isolation procedure of MSCs is approximately a 4-week process6; too long to be feasible in a surgical environment.
Plastic & Reconstructive Surgery
Plastic and Aesthetic Research
Autologous fat grafting is an important surgical technique in aesthetic and reconstructive proced... more Autologous fat grafting is an important surgical technique in aesthetic and reconstructive procedures. Fat grafting for breast reconstruction is now an established procedure for adding volume and improving cutaneous pliability; it can be used independently to replace more invasive flap procedures or implants, or as an adjunct for smaller volume supplementation. The breadth of applications in the breast necessitates diversity in technique and approach, and while there is no universally agreed-upon protocol, basic principles have guided the evolution of some commonly adopted tenets. Broadly, fat grafting outcomes are highly favorable but dependent on patient and procedure factors, requiring learned patient selection and expertise in recipient site assessment. Common complications from fat grafting, such as fat necrosis and the development of nodules, are particularly troublesome for post-oncologic patients, requiring considerable pre-surgical consultation for patient education and man...
Aesthetic Surgery Journal
Background Autologous fat grafting, although broadly indicated, is limited by unsatisfactory rete... more Background Autologous fat grafting, although broadly indicated, is limited by unsatisfactory retention and often requires multiple procedures to achieve durable outcomes. Graft survival is strongly influenced by the magnitude and duration of post-engraftment ischemia. Calcitriol is a pleiotropic, safe nutrient with cell-specific influence on viability and metabolic flux. Objectives Evaluate the efficacy of activated vitamin D3 (calcitriol) in improving grafting outcomes and examine its mechanisms. Methods Lipoaspirate was collected for ex vivo culture (7 unique donors), in vitro bioenergetic analysis (6 unique donors), and in vivo transplantation (5 unique donors). Ex vivo samples were incubated for up to 2 weeks before extraction of the stromal vascular fraction (SVF) for viability or flow cytometry. SVF was collected for Seahorse (Agilent; Santa Clara, CA) analysis of metabolic activity. Human endothelial cell lines were utilized for analyses of endothelial function. In vivo, samp...
Facial Plastic Surgery & Aesthetic Medicine
Stem Cells and Development
Adipose therapeutics, including isolated cell fractions and tissue emulsifications, have been exp... more Adipose therapeutics, including isolated cell fractions and tissue emulsifications, have been explored for osteoarthritis (OA) treatment, however the optimal preparation method and bioactive tissue component for healing has yet to be determined. This in-vitro study compared the effects of adipose preparations on cultured knee chondrocytes. De-identified human articular chondrocytes were co-cultured with adipose preparations for 36 or 72 hours. Human adipose tissues were obtained from abdominal panniculectomy procedures and processed using three different techniques: enzymatic digestion to release stromal vascular fraction (SVF), emulsification with luer-to-luer transfer (nanofat), and processing in a bead-mill (Lipogems, Lipogems International SpA, Milan, Italy). Gene expression in both chondrocytes and adipose preparations was measured to assess cellular inflammation, catabolism, and anabolism. Results demonstrated that chondrocytes cultured with SVF consistently showed increased inflammatory and catabolic gene expression compared to control chondrocytes at both 36-and 72-hour timepoints. Alternatively, chondrocytes co-cultured with either nanofat or bead-mill processed adipose derivatives yielded minimal pro-inflammatory effects and instead increased anabolism and regeneration of cartilage extracellular matrix. Interestingly, nanofat preparations induced transient matrix anabolism while Lipogems adipose consistently demonstrated increased matrix synthesis at both study time points following co-culture. This evaluation of the regenerative potential of adipose-derived preparations as a clinical tool for knee OA treatment suggests that mechanically processed preparations may be more efficacious than an isolated SVF cell preparation.
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Plastic and Reconstructive Surgery - Global Open
Journal of Burn Care & Research, Mar 23, 2022
Introduction: Adipose and adipose-derived stem cell therapies have met success as adjunctive trea... more Introduction: Adipose and adipose-derived stem cell therapies have met success as adjunctive treatment during burn reconstruction with well described benefit in the delayed-treatment of soft-tissue deficits. While the use of allogeneic skin is well-described, adipose tissues have typically remained autologous. Allogenic fat is not commonly used in burn care, however, in large, complex burns where autologous tissue is limited adipose may not be readily available for harvest or use. Understanding the efficacy of allogeneic tissues in this setting is critical to expand our reconstructive options. Here we describe a protocol utilizing allogeneic fat as well as examine the efficacy of this approach on burn-wound contractures, adhesions, and soft-tissue deficits. Methods: Female, Yorkshire swine received 16, 4x4 cm full-thickness burns. After 48 hours, eschar was removed to fascia. Wounds were stratified to receive either A) No Reconstruction, B) Skin-Only, C) Fat-Only, D) Immediate-Skin, Delayed-Fat, or E) Immediate-Fat, Delayed-Skin. All fat utilized was allogeneic sourced from vendor-matched swine. At 8-weeks post-engraftment animals were sacrificed and all wounds were collected for photography, ultrasound, histology and serum studies. Results: Use of allogeneic fat significantly improved terminal soft-tissue thickness under both immediate and delayed administration (p< 0.05). Immediate use of allogeneic fat significantly improved tissue mobility vs. untreated and skin graft controls (p< 0.05). Contracture was most significantly affected by timing of skin graft placement, however, could be further mitigated under standard delayed-fat approached with allogeneic tissue. Conclusions: Here we demonstrate use of allogeneic fat in both traditional-delayed and a fat-first approach with significant mitigation of adhesion when applied as an initial basal layer. Both immediate and delayed allogeneic fat were sufficient to improve on soft tissue deficits.
Plastic and Reconstructive Surgery - Global Open, 2022
Plastic and Reconstructive Surgery Global Open, 2017
METHODS: Collagenase derived from Clostridium Histolyticum was used in a randomized, double-blind... more METHODS: Collagenase derived from Clostridium Histolyticum was used in a randomized, double-blinded, placebo controlled study on a total of 19 healthy subjects, each with two biopsy-proven lipomas of similar size (one to receive drug and one to receive placebo) at two independent investigational centers (Office of Z. Gerut and Dept. of Plastic Surgery Vanderbilt Univ. Med Ctr.). An independent pharmacist prepared the research drug and the placebo for injection and the two indiscernible preparations were randomized for injection into the two lipomas of each subject; all staff including the investigators, as well as the subject were blinded.
Acta Pharmaceutica Sinica B, 2021
PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute l... more PEGylated-l-asparaginase (PEG-ASNase) is a chemotherapeutic agent used to treat pediatric acute lymphoblastic leukemia (ALL). Its use is avoided in adults due to its high risk of liver injury including hepatic steatosis, with obesity and older age considered risk factors of the injury. Our study aims to elucidate the mechanism of PEG-ASNase-induced liver injury. Mice received 1500 U/kg of PEG-ASNase and were sacrificed 1, 3, 5, and 7 days after drug administration. Liver triglycerides were quantified, and plasma bilirubin, ALT, AST, and non-esterified fatty acids (NEFA) were measured. The mRNA and protein levels of genes involved in hepatic fatty acid synthesis, β-oxidation, very low-density lipoprotein (VLDL) secretion, and white adipose tissue (WAT) lipolysis were determined. Mice developed hepatic steatosis after PEG-ASNase, which associated with increases in bilirubin, ALT, and AST. The hepatic genes Ppara, Lcad/Mcad, Hadhb, Apob100, and Mttp were upregulated, and Srebp-1c and Fas were downregulated after PEG-ASNase. Increased plasma NEFA, WAT loss, and adipose tissue lipolysis were also observed after PEG-ASNase. Furthermore, we found that PEG-ASNase-induced liver injury was exacerbated in obese and aged mice, consistent with clinical studies of ASNase-induced liver injury. Our data suggest that PEG-ASNase-induced liver injury is due to drug-induced lipolysis and lipid redistribution to the liver.
19. Chiaki Komatsu, Yolandi van der Merwe, Lin He, Maxine R. Miller, Katie A. Lucy, Huamin Tang, ... more 19. Chiaki Komatsu, Yolandi van der Merwe, Lin He, Maxine R. Miller, Katie A. Lucy, Huamin Tang, Ian Rosner, Wendy Chen, Jila Noori, Valeria Fu, Michael Steketee, Gadi Wollstein, Mario Solari, Joel S. Schuman, Kevin C. Chan, Kia M. Washington. Retinal and optic nerve viability evaluated with optical coherence tomography, manganese-enhanced MRI and electroretinography after whole eye transplantation
INTRODUCTION Tissue engineered vascular grafts (TEVGs) seeded with autologous cells offer a treat... more INTRODUCTION Tissue engineered vascular grafts (TEVGs) seeded with autologous cells offer a treatment alternative to current coronary artery by-pass procedures1-4. Past work has demonstrated that TEVGs seeded with only a mesenchymal stem cell (MSC) population will remodel in vivo5. However, the isolation procedure of MSCs is approximately a 4-week process6; too long to be feasible in a surgical environment.