Lacell, Llc

BATON ROUGE, LA, United States

Lacell, Llc

BATON ROUGE, LA, United States

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Gimble J.M.,Pennington Biomedical Research Center | Gimble J.M.,Lacell, Llc | Gimble J.M.,Tulane University | Bunnell B.A.,Lacell, Llc | And 5 more authors.
Organogenesis | Year: 2013

Until recently, the complexity of adipose tissue and its physiological role was not well appreciated. This changed with the discovery of adipokines such as leptin. The cellular composition of adipose tissue is heterogeneous and changes as a function of diabetes and disease states such as diabetes. Tissue engineers view adipose tissue as a rich source of adult stromal/stem cells isolated by collagenase digestion. In vitro and in vivo studies have documented that adipose stromal/stem cells are multipotent, with the ability to differentiate along the adipocyte, chondrocyte, osteoblast and other lineage pathways. The adipose stromal/stem cells secrete a wide range of cytokines and growth factors with potential paracrine actions. Furthermore, adipose stromal/stem cells exert immunomodulatory functions when added to mixed lymphocyte reactions, suggesting that they can be transplanted allogeneically. This review article focuses on these mechanisms of adipose stromal/stem cell action and their potential utility as cellular therapeutics. © 2013 Landes Bioscience.


Tran T.D.N.,Louisiana State University | Gimble J.M.,Lacell, Llc | Cheng H.,Louisiana State University
Cell Calcium | Year: 2016

Intracellular Ca2+ signals are essential for stem cell differentiation due to their ability to control signaling pathways involved in this process. Arginine vasopression (AVP) is a neurohypophyseal hormone that increases intracellular Ca2+ concentration during adipogenesis via V1a receptors, Gq-proteins and the PLC-IP3 pathway in human adipose-derived stromal/stem cells (hASCs). These Ca2+ signals originate through calcium release from pools within the endoplasmic reticulum and the extracellular space. AVP supplementation to the adipogenic media inhibits adipogenesis and key adipocyte marker genes. This review focuses on the intersection between AVP, Ca2+ signals and ASC differentiation. © 2016 Elsevier Ltd.


Tran T.D.N.,Louisiana State University | Zolochevska O.,University of Texas Medical Branch | Figueiredo M.L.,University of Texas Medical Branch | Wang H.,University of Florida | And 4 more authors.
Biochemical Journal | Year: 2014

Intracellular Ca2+oscillations are frequently observed during stem cell differentiation, and there is evidence that it may control adipogenesis. The transient receptor potential melastatin 4 channel (TRPM4) is a key regulator of Ca2+signals in excitable and non-excitable cells. However, its role in human adiposederived stem cells (hASCs), in particular during adipogenesis, is unknown. We have investigated TRPM4 in hASCs and examined its impact on histamine-induced Ca2+signalling and adipogenesis. Using reverse transcription (RT)-PCR, we have identified TRPM4 gene expression in hASCs and human adipose tissue. Electrophysiological recordings revealed currents with the characteristics of those reported for the channel. Furthermore, molecular suppression of TRPM4 with shRNA diminished the Ca2+signals generated by histamine stimulation, mainly via histamine receptor 1 (H1) receptors. The increases in intracellular Ca2+were due to influx via voltage-dependent Ca2+channels (VDCCs) of the L-type (Cav1.2) and release from the endoplasmic reticulum. Inhibition of TRPM4by shRNAinhibited adipogenesis as indicated by the reduction in lipid droplet accumulation and adipocyte gene expression. These results suggest that TRPM4 is an important regulator of Ca2+signals generated by histamine in hASCs and is required for adipogenesis. © 2014 Biochemical Society.


Qureshi A.T.,Louisiana State University | Chen C.,Louisiana State University | Shah F.,Lacell, Llc | Thomas-Porch C.,Tulane University | And 2 more authors.
Methods in Enzymology | Year: 2014

Annually, more than 200,000 elective liposuction procedures are performed in the United States and over a million worldwide. The ease of harvest and abundance make human adipose-derived stromal/stem cells (hASCs) isolated from lipoaspirates an attractive, readily available source of adult stem cells that have become increasingly popular for use in many studies. Here, we describe common methods for hASC culture, preservation, and osteogenic differentiation. We introduce methods of ceramic, polymer, and composite scaffold synthesis with a description of morphological, chemical, and mechanical characterization techniques. Techniques for scaffold loading are compared, and methods for determining cell loading efficiency and proliferation are described. Finally, we provide both qualitative and quantitative techniques for in vitro assessment of hASC osteogenic differentiation. © 2014 Elsevier Inc.


Yilgor Huri P.,Johns Hopkins University | Cook C.A.,Johns Hopkins University | Hutton D.L.,Johns Hopkins University | Goh B.C.,Johns Hopkins University | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Adipose-derived stem/stromal cell (ASC)-based tissue engineered muscle grafts could provide an effective alternative therapy to autografts - which are limited by their availability - for the regeneration of damaged muscle. However, the current myogenic potential of ASCs is limited by their low differentiation efficiency into myoblasts. The aim of this study was to enhance the myogenic response of human ASCs to biochemical cues by providing biophysical stimuli (11% cyclic uniaxial strain, 0.5. Hz, 1. h/day) to mimic the cues present in the native muscle microenvironment. ASCs elongated and fused upon induction with myogenic induction medium alone. Yet, their myogenic characteristics were significantly enhanced with the addition of biophysical stimulation; the nuclei per cell increased approximately 4.5-fold by day 21 in dynamic compared to static conditions (23.3 ± 7.3 vs. 5.2 ± 1.6, respectively), they aligned at almost 45° to the direction of strain, and exhibited significantly higher expression of myogenic proteins (desmin, myoD and myosin heavy chain). These results demonstrate that mimicking the biophysical cues inherent to the native muscle microenvironment in monolayer ASC cultures significantly improves their differentiation along the myogenic lineage. © 2013 Elsevier Inc.


Strong A.L.,Tulane University | Burow M.E.,Tulane University | Gimble J.M.,Tulane University | Bunnell B.A.,Tulane University | Bunnell B.A.,Lacell, Llc
Stem Cells | Year: 2015

With the recognition of obesity as a global health crisis, researchers have devoted greater effort to defining and understanding the pathophysiological molecular pathways regulating the biology of adipose tissue and obesity. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, has been linked to an increased incidence and aggressiveness of colon, hematological, prostate, and postmenopausal breast cancers. The increased morbidity and mortality of obesity-associated cancers have been attributed to higher levels of hormones, adipokines, and cytokines secreted by the adipose tissue. The increased amount of adipose tissue also results in higher numbers of adipose stromal/stem cells (ASCs). These ASCs have been shown to impact cancer progression directly through several mechanisms, including the increased recruitment of ASCs to the tumor site and increased production of cytokines and growth factors by ASCs and other cells within the tumor stroma. Emerging evidence indicates that obesity induces alterations in the biologic properties of ASCs, subsequently leading to enhanced tumorigenesis and metastasis of cancer cells. This review will discuss the links between obesity and cancer tumor progression, including obesity-associated changes in adipose tissue, inflammation, adipokines, and chemokines. Novel topics will include a discussion of the contribution of ASCs to this complex system with an emphasis on their role in the tumor stroma. The reciprocal and circular feedback loop between obesity and ASCs as well as the mechanisms by which ASCs from obese patients alter the biology of cancer cells and enhance tumorigenesis will be discussed. © 2014 AlphaMed Press.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 617.59K | Year: 2016

DESCRIPTION provided by applicant This Phase II SBIR extends a Phase I proof of principle study originally submitted in response to RFA AG entitled andquot T Translational Research on Agingandquot from the NIA In Phase I LaCell has documented pre clinical safety and efficacy of a novel adipose derived cell therapy for the treatment of pressure ulcers in young and old mice The injection of murine ASC significantly accelerated and enhanced pressure ulcer repair in female mice of both age groups in a dose dependent manner as evidenced by the rate of wound closure re epithelialization skin tissue architecture inflammatory cell infiltratin and expression of molecular biomarkers LaCellandapos s studies pave the way for clinical translation and regulatory approval of ASC therapies While it is well established that the prevention of pressure ulcers requires labor intensive nursing care patients in assisted living centers and nursing homes remain at high risk for developing pressure ulcers Over of pressure ulcers occur in Americans over the age of and their hospital costs exceed $ billion annually Current treatment of pressure ulcers relies primarily on surgical debridement hyperbaric oxygen and negative pressure devices The adipose derived cell based therapies have the potential to substantially reduce the length of hospitalization and associated health care costs for pressure ulcer patients LaCell has partnered with a Tissue Genesis Inc to use their established ICellator device to obtain clinical grade human SVF cells This strategic partnership will accelerate the clinical translation of LaCellandapos s cell therapeutic to the marketplace Specific Aims SA will address pharmacotoxicology regulatory concerns in murine models and serve as a definitive protocol to the Food and Drug Administration for an Investigational Device Exemption in the case of SVF cells SA and a Biologics License Application in the case of ASC SA Each SA will evaluate the concentration dependency of human SVF cells and ASC in the treatment of a murine pressure ulcer therapy in immunodeficient and immunocompetent mice of both sexes both young and old immunocompetent mice will be evaluated Injection of PBS alone or with human dermal fibroblasts will serve as negative controls while topical application of the FDA approved diabetic wound therapeutic beclapermin PDGF BB will serve as a positive control Quantitative outcomes will include rate of wound closure inflammatory cell infiltration pro inflammatory cytokine expression and immunohistochemical detection of human cells in situ Since pressure ulcer treatment accounts for of the total health care budget in developed nations LaCellandapos s developing technologies have considerable market potential PUBLIC HEALTH RELEVANCE The elderly are at high risk for the development of pressure ulcers a life threatening condition that remains a major health care burden in the U S With its background in adipose stromal stem cell biotechnology LaCell its strategic partner Tissue Genesis Inc and its academic collaborators are uniquely positioned to address this unmet medical need LaCell has peer review published Preliminary Data supporting the efficacy and safety of an adipose stromal stem cell therapy for pressure ulcers LaCellandapos s approach has the potential to accelerate and improve the rate of wound closure and long term recovery This Phase II proposal will extend on LaCellandapos s initial findings and develop essential pre clinical data to advance adipose derived cell therapies and translate them into an FDA approved clinical trial LaCellandapos s stem cell products are relevant to geriatric medicine and will improve healthcare for the rapidly growing number of elderly Americans


Grant
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2016

The broader impact/commercial potential of this Small Business Innovative Research (SBIR) project will be to provide the biotechnology and pharmaceutical research community with improved models that will accelerate the discovery of the next generation of drugs targeting fat metabolism. Currently, over one in every three American adults are obese and the incidence of childhood obesity continues to climb. Obesity is now recognized as a world-wide epidemic which will impact many if not all nations. In the coming decades, it will be critical to develop more effective therapies for obesity and its associated problems, diabetes, heart disease, high blood pressure and stroke. Obesity is caused by an overgrowth of the body's fat cells. Unlike current models that rely heavily on mouse fat cells, the proposed "humanized fat-on-a-chip" technology will provide scientists with a research model that closely approximates the clinical conditions that face doctors and their patients every day. By working with human fat cells in a three dimensional structure resembling the actual human tissue, the proposed platform has the potential to impact the pace of new drug discovery and the cost of health care delivery for disease prevention and treatment. This SBIR project proposes to develop a "humanized fat-on-a-chip" drug discovery platform targeting drugs for fat metabolism. The pharmaceutical industry currently lacks a robust human fat tissue model, and continues to use less reliable mouse models. As a result, the obesity and diabetes drug discovery pipeline remains blocked. To address this need, the proposed project will combine human cells with protein scaffolds to pioneer a tissue engineered fat pad. The objectives are to 1) evaluate the human cells and scaffolds separately to confirm the identity and function; 2) combine the human cells with the scaffold and perform assays in vitro to demonstrate that they can mimic the function of actual human fat; and 3) transplant the human cell/scaffold constructs into mice for 8 weeks to show that the tissue engineered fat pad will work under "real life" conditions. It is anticipated that the human cell/scaffold constructs will display the metabolic features associated with human fat. With this proof-of-concept data, the next step will be to create tissue engineered fat pads that display not only healthy but unhealthy (diabetes, obesity) metabolic patterns for use in drug screening and discovery.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 185.96K | Year: 2012

DESCRIPTION (provided by applicant): This Phase I SBIR, responding to RFA-AG-12-009 entitled T1 Translational Research on Aging from the NIA, explores novel cell-based therapeutic approaches to the treatment of pressure ulcers and full thickness skin wounds in the elderly. Although it is well established that the prevention of pressure ulcers requires labor- intensive nursing care, patients in assisted living centers and nursing homes remain at high risk for developing pressure ulcers. In fact, over 70%of pressure ulcers occur in Americans over the age of 70 and their hospital costs exceed 11 billion annually. Current treatment of pressure ulcers relies primarily on surgical debridement, hyperbaric oxygen, growth factors, and negative pressure devices.This proof of principle study will use a murine model to test LaCell's hypothesis that adipose-derived stromal/stem cell (ASC) therapy will accelerate and improve pressure ulcer healing in the elderly. Studies will be conducted in young (3-4 month) and old (24 month) C57Bl/6 male mice using leptin receptor deficient (db/db) obese diabetic mice (3-4 month) as positive controls. Bilateral full thickness skin wounds will be created dorsally on each mouse. These will be protected by a silicon splint in theshape of a donut to prevent spontaneous retraction of the wound edges. This will allow for accurate measurements of the wound epithelialization and healing rates. Adipose stromal/stem cells (ASC) will be isolated from C57Bl/6 mice transgenic for the greenfluorescent protein (GFP). In each animal, GFP+ ASC will be injected into the wound bed of one full thickness defect while the corresponding wound, injected with phosphate buffered saline, will serve as a control. Groups of animals will be harvested after1, 3, and 10 days post-operatively. Quantitative experimental outcomes will address the mechanisms underlying the ASC impact on repair that will include rates of epithelialization, wound closure, cytokine and matrix metalloproteinase expression, and immune cell infiltration. These outcomes will determine the feasibility and efficacy of ASC based therapies to accelerate the repair of pressure ulcers and full thickness skin wounds in the elderly. Phase I will lay the foundation for future pharmacokinetic andtoxicological testing of both murine and human ASC in Phase II studies. Additionally, they will provide the basis for detailed pre-IND discussions with the Food and Drug Administration. LaCell LLC is a biotechnology company founded by leading investigators and inventors in the application of adipose stromal/stem cells to regenerative medicine. As consultants, LaCell has enlisted the assistance of experts in the field of plastic surgery and wound healing. PUBLIC HEALTH RELEVANCE: The elderly are athigh risk for the development of pressure ulcers, a debilitating and life threatening condition that remains a major health care burden in the U.S. LaCell proposes to develop an adipose stromal/stem cell therapy for pressure ulcers. This approach has thepotential to accelerate and improve the rate of wound closure and long-term recovery. The outcomes of this focused proof of principle pre-clinical study have relevance to a clinical issue of unique importance to geriatric medicine in the U.S. and abroad. With its background in adipose stromal/stem cell biotechnology, LaCell and its consultants are uniquely positioned to address this unmet medical need.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE I | Award Amount: 225.00K | Year: 2016

The broader impact/commercial potential of this Small Business Innovative Research (SBIR) project will be to provide the biotechnology and pharmaceutical research community with improved models that will accelerate the discovery of the next generation of drugs targeting fat metabolism. Currently, over one in every three American adults are obese and the incidence of childhood obesity continues to climb. Obesity is now recognized as a world-wide epidemic which will impact many if not all nations. In the coming decades, it will be critical to develop more effective therapies for obesity and its associated problems, diabetes, heart disease, high blood pressure and stroke. Obesity is caused by an overgrowth of the bodys fat cells. Unlike current models that rely heavily on mouse fat cells, the proposed humanized fat-on-a-chip technology will provide scientists with a research model that closely approximates the clinical conditions that face doctors and their patients every day. By working with human fat cells in a three dimensional structure resembling the actual human tissue, the proposed platform has the potential to impact the pace of new drug discovery and the cost of health care delivery for disease prevention and treatment.

This SBIR project proposes to develop a humanized fat-on-a-chip drug discovery platform targeting drugs for fat metabolism. The pharmaceutical industry currently lacks a robust human fat tissue model, and continues to use less reliable mouse models. As a result, the obesity and diabetes drug discovery pipeline remains blocked. To address this need, the proposed project will combine human cells with protein scaffolds to pioneer a tissue engineered fat pad. The objectives are to 1) evaluate the human cells and scaffolds separately to confirm the identity and function; 2) combine the human cells with the scaffold and perform assays in vitro to demonstrate that they can mimic the function of actual human fat; and 3) transplant the human cell/scaffold constructs into mice for 8 weeks to show that the tissue engineered fat pad will work under real life conditions. It is anticipated that the human cell/scaffold constructs will display the metabolic features associated with human fat. With this proof-of-concept data, the next step will be to create tissue engineered fat pads that display not only healthy but unhealthy (diabetes, obesity) metabolic patterns for use in drug screening and discovery.

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