Sex hormones strongly influence skin physiology and evidences suggest wound healing as well. Estr... more Sex hormones strongly influence skin physiology and evidences suggest wound healing as well. Estrogens establish a prohealing setting, and androgens play an antagonist role. We present the case of a young woman in whom pregnancy with its associated hormonal shifts allowed the spontaneous healing of a chronic wound on the left leg with bone exposure, which had followed a car accident and had resisted medical and surgical treatments for 5 years. Systemic or topical estrogens may offer alternative options in the therapy of chronic wounds, in particular in the elderly adults who have physiologically reduced estrogens levels.
Necrotizing fasciitis (NF), a life-threatening rare infection of the soft tissues, is a medical a... more Necrotizing fasciitis (NF), a life-threatening rare infection of the soft tissues, is a medical and surgical emergency. It is characterized by subtle, rapid onset of spreading inflammation and necrosis starting from the fascia, muscles, and subcutaneous fat, with subsequent necrosis of the overlying skin. Once suspected, immediate and extensive radical debridement of necrotic tissues is mandatory. Appropriate antibiotics and intensive general support avoid massive systemic diffusion of the infective process and are the key for successful treatment. However, early diagnosis is missed or delayed in 85% to 100% of cases in large published series: because of the lack of specific clinical features in the initial stage of the disease, it is often underestimated or confused with cellulitis or abscess. Mortality rates are still high and have shown no tendency to decrease in the last 100 years. Unfortunately, the prevalence of the disease is such that physicians rarely become sufficiently confident with NF to be able to proceed with rapid diagnosis and management. This review covers the literature published in MEDLINE in the period 1970 to December 31, 2010. Particular attention is given to the clinical and laboratory elements to be considered for diagnosis. A wide variety of diagnostic tools have been described to facilitate and hasten the diagnosis of NF, but the most important tool for early diagnosis still remains a high index of clinical suspicion.
A significant amount of recent interest has been focused on the possibility that adult human stem... more A significant amount of recent interest has been focused on the possibility that adult human stem cells are a realistic therapeutic alternative to embryonic stem cells. Multipotent stem cells that have characteristics reminiscent of embryonic neural crest stem cells have been isolated from several postnatal tissues, including skin, gut, dental pulp and the heart, and are potentially useful for research and therapeutic purposes. However, their neurogenic potential, including their ability to produce electrophysiologically active neurons, is largely unexplored. In the present work, we investigated this issue with regard to skin-derived precursors (SKPs) and adipose-derived stem cells (ADSc) Adult stem cells isolated from skin and from adipose tissue derived from the same adult donor were treated with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Neurospheres obtained were first expanded and evaluated in term of proliferative ability, and then their neuronal differentiation potential was analysed. Adipose- and skin-derived neurospheres grew in suspension as spheres in the presence of the mitogens FGF2 and EGF. With this protocols, the spheres have been able to proliferate and to originate Schwann and glial-like cells. In summary, we have demonstrated in this work that multipotent adult precursor cell can be isolated and expanded from two accessible adult tissue sources: skin and adipose tissue. The work described in this paper provides the framework for our attempts to use SKPs or ADSc as autologous adult stem cell population for cell replacement and discovery research.
The Journal of Trauma: Injury, Infection, and Critical Care, 2011
Skin burns are an acute trauma involving an extensive vascular damage and an intense inflammatory... more Skin burns are an acute trauma involving an extensive vascular damage and an intense inflammatory response. Bone marrow-derived circulating endothelial progenitor cells (EPC) are known to migrate to sites of neovascularization in response to mediators (vascular endothelial growth factor and stromal cell-derived factor-1) released after trauma and ischemia, to contribute to wound healing, and to increase neovascularization of animal prefabricated flaps. Recent data showed an increase in EPC number in burned patients and a positive correlation between EPC number and total body surface area (TBSA) burnt, but data were limited to the first 5 days after thermal injury. By using flow cytometry, we studied EPC (CD34, CD133, CD45, and KDR cells) blood levels, apoptosis, and homing (stromal cell-derived factor-1 receptor expression and CXC chemokine receptor 4) in a 1-month follow-up postburn in 25 patients with ≥15% TBSA burnt, at least grade II burns and escharectomy performed at days 5 to 6, with respect to 31 controls. EPC count at admission showed a positive linear correlation with TBSA burnt. The EPC blood levels of the patients were low (50.7 cells/mL±61.8 cells/mL) immediately after thermal injury, then increased with two peaks, at day 1 (188.3 cells/mL±223.2 cells/mL) and day 12 (253.1 cells/mL±430.7 cells/mL) with respect to controls (95.2 cells/mL±28.5 cells/mL, p<0.05), and then returned to normal levels in 1 month. EPC apoptotic rate and inflammatory parameters paralleled EPC blood count. No significant variations were found in CXC chemokine receptor 4 expression. Thermal injury and escharectomy seem to induce an intense response in EPC production. In particular, escharectomy could improve physiologic wound repair by increasing EPC levels.
A greater supply of tendinous tissue can be obtained through tissue engineering technology with i... more A greater supply of tendinous tissue can be obtained through tissue engineering technology with increasing application of adult stem cells. It is well known that adipose-derived stem cells (ADSCs), found in abundance in adipose tissue, have the same differentiating capacity as mesenchymal stem cells yet have the advantage of being easily isolated. In the present study, we combined the great facility of ADSCs to differentiate with the application of an external mechanical stimulus to successfully create an in vitro reconstructed tendonlike structure with a microcapillary network. Hyalonect meshes (Fidia Advanced Biopolymers, Abano Terme, Padova, Italy) were used as scaffold. Human ADSCs were seeded onto the biomaterials, and the cell/scaffold constructs were cultured under mechanical stress for up to 15 days. Human tenocytes were used in the same conditions as control. Performance was assessed by histology, immunochemistry, ultrastructure, and biomolecular analysis. Adipose-derived stem cells seeded onto Hyalonect adhered and differentiated along the entire surface of the biomaterial and began to infiltrate within its structure. Subsequently, endothelial cells migrated, forming a capillary in the new extracellular matrix. This technique allowed for the creation of a vascularized tendon equivalent that could easily be detached from the bioreactor, thus facilitating its implant at the lesion site. These results highlight the biologic performance of biodegradable hyaluronic acid-based (HYAFF-11) scaffolds, which were shown to be suitable for deposition of the autologous extracellular matrix critical for ADSCs differentiation.
OBJECTIVE: In recent years, research on stem cells has been focused on the development of persona... more OBJECTIVE: In recent years, research on stem cells has been focused on the development of personalized cell-based therapies. Owing to their homing properties, adult human stem cells are a promising source of autologous cells to be used as therapeutic vehicles. Multiple potential sources for clinically useful stem and progenitor cells have been identified, including autologous and allogenic embryonic, fetal and adult somatic cells from neural, adipose and mesenchymal tissue. In the present report, we describe a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. METHODS: Adult stem cells isolated from skin and adipose tissue derived from the same adult donor were amplified under varying conditions related to the coating of the chamber slide and the presence of serum and/or growth factors, such as with EGF and FGF2. Neurospheres were then expanded and evaluated in terms of proliferation and gene expression. RESULTS: Adipose and skin derived neurospheres were comparable in size, quantity of cells and genes expressed. Cells from both types of tissue grew optimally without slide coating, in the presence of serum and with the combined addition of FGF2 and EGF. DISCUSSION: We describe a method for isolating and improving a population of multipotent adult precursor cells from the two most accessible adult tissue sources: skin and adipose tissue. This autologous adult stem cell population could be used for cell replacement or cell therapies.
Sex hormones strongly influence skin physiology and evidences suggest wound healing as well. Estr... more Sex hormones strongly influence skin physiology and evidences suggest wound healing as well. Estrogens establish a prohealing setting, and androgens play an antagonist role. We present the case of a young woman in whom pregnancy with its associated hormonal shifts allowed the spontaneous healing of a chronic wound on the left leg with bone exposure, which had followed a car accident and had resisted medical and surgical treatments for 5 years. Systemic or topical estrogens may offer alternative options in the therapy of chronic wounds, in particular in the elderly adults who have physiologically reduced estrogens levels.
Necrotizing fasciitis (NF), a life-threatening rare infection of the soft tissues, is a medical a... more Necrotizing fasciitis (NF), a life-threatening rare infection of the soft tissues, is a medical and surgical emergency. It is characterized by subtle, rapid onset of spreading inflammation and necrosis starting from the fascia, muscles, and subcutaneous fat, with subsequent necrosis of the overlying skin. Once suspected, immediate and extensive radical debridement of necrotic tissues is mandatory. Appropriate antibiotics and intensive general support avoid massive systemic diffusion of the infective process and are the key for successful treatment. However, early diagnosis is missed or delayed in 85% to 100% of cases in large published series: because of the lack of specific clinical features in the initial stage of the disease, it is often underestimated or confused with cellulitis or abscess. Mortality rates are still high and have shown no tendency to decrease in the last 100 years. Unfortunately, the prevalence of the disease is such that physicians rarely become sufficiently confident with NF to be able to proceed with rapid diagnosis and management. This review covers the literature published in MEDLINE in the period 1970 to December 31, 2010. Particular attention is given to the clinical and laboratory elements to be considered for diagnosis. A wide variety of diagnostic tools have been described to facilitate and hasten the diagnosis of NF, but the most important tool for early diagnosis still remains a high index of clinical suspicion.
A significant amount of recent interest has been focused on the possibility that adult human stem... more A significant amount of recent interest has been focused on the possibility that adult human stem cells are a realistic therapeutic alternative to embryonic stem cells. Multipotent stem cells that have characteristics reminiscent of embryonic neural crest stem cells have been isolated from several postnatal tissues, including skin, gut, dental pulp and the heart, and are potentially useful for research and therapeutic purposes. However, their neurogenic potential, including their ability to produce electrophysiologically active neurons, is largely unexplored. In the present work, we investigated this issue with regard to skin-derived precursors (SKPs) and adipose-derived stem cells (ADSc) Adult stem cells isolated from skin and from adipose tissue derived from the same adult donor were treated with epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2). Neurospheres obtained were first expanded and evaluated in term of proliferative ability, and then their neuronal differentiation potential was analysed. Adipose- and skin-derived neurospheres grew in suspension as spheres in the presence of the mitogens FGF2 and EGF. With this protocols, the spheres have been able to proliferate and to originate Schwann and glial-like cells. In summary, we have demonstrated in this work that multipotent adult precursor cell can be isolated and expanded from two accessible adult tissue sources: skin and adipose tissue. The work described in this paper provides the framework for our attempts to use SKPs or ADSc as autologous adult stem cell population for cell replacement and discovery research.
The Journal of Trauma: Injury, Infection, and Critical Care, 2011
Skin burns are an acute trauma involving an extensive vascular damage and an intense inflammatory... more Skin burns are an acute trauma involving an extensive vascular damage and an intense inflammatory response. Bone marrow-derived circulating endothelial progenitor cells (EPC) are known to migrate to sites of neovascularization in response to mediators (vascular endothelial growth factor and stromal cell-derived factor-1) released after trauma and ischemia, to contribute to wound healing, and to increase neovascularization of animal prefabricated flaps. Recent data showed an increase in EPC number in burned patients and a positive correlation between EPC number and total body surface area (TBSA) burnt, but data were limited to the first 5 days after thermal injury. By using flow cytometry, we studied EPC (CD34, CD133, CD45, and KDR cells) blood levels, apoptosis, and homing (stromal cell-derived factor-1 receptor expression and CXC chemokine receptor 4) in a 1-month follow-up postburn in 25 patients with ≥15% TBSA burnt, at least grade II burns and escharectomy performed at days 5 to 6, with respect to 31 controls. EPC count at admission showed a positive linear correlation with TBSA burnt. The EPC blood levels of the patients were low (50.7 cells/mL±61.8 cells/mL) immediately after thermal injury, then increased with two peaks, at day 1 (188.3 cells/mL±223.2 cells/mL) and day 12 (253.1 cells/mL±430.7 cells/mL) with respect to controls (95.2 cells/mL±28.5 cells/mL, p<0.05), and then returned to normal levels in 1 month. EPC apoptotic rate and inflammatory parameters paralleled EPC blood count. No significant variations were found in CXC chemokine receptor 4 expression. Thermal injury and escharectomy seem to induce an intense response in EPC production. In particular, escharectomy could improve physiologic wound repair by increasing EPC levels.
A greater supply of tendinous tissue can be obtained through tissue engineering technology with i... more A greater supply of tendinous tissue can be obtained through tissue engineering technology with increasing application of adult stem cells. It is well known that adipose-derived stem cells (ADSCs), found in abundance in adipose tissue, have the same differentiating capacity as mesenchymal stem cells yet have the advantage of being easily isolated. In the present study, we combined the great facility of ADSCs to differentiate with the application of an external mechanical stimulus to successfully create an in vitro reconstructed tendonlike structure with a microcapillary network. Hyalonect meshes (Fidia Advanced Biopolymers, Abano Terme, Padova, Italy) were used as scaffold. Human ADSCs were seeded onto the biomaterials, and the cell/scaffold constructs were cultured under mechanical stress for up to 15 days. Human tenocytes were used in the same conditions as control. Performance was assessed by histology, immunochemistry, ultrastructure, and biomolecular analysis. Adipose-derived stem cells seeded onto Hyalonect adhered and differentiated along the entire surface of the biomaterial and began to infiltrate within its structure. Subsequently, endothelial cells migrated, forming a capillary in the new extracellular matrix. This technique allowed for the creation of a vascularized tendon equivalent that could easily be detached from the bioreactor, thus facilitating its implant at the lesion site. These results highlight the biologic performance of biodegradable hyaluronic acid-based (HYAFF-11) scaffolds, which were shown to be suitable for deposition of the autologous extracellular matrix critical for ADSCs differentiation.
OBJECTIVE: In recent years, research on stem cells has been focused on the development of persona... more OBJECTIVE: In recent years, research on stem cells has been focused on the development of personalized cell-based therapies. Owing to their homing properties, adult human stem cells are a promising source of autologous cells to be used as therapeutic vehicles. Multiple potential sources for clinically useful stem and progenitor cells have been identified, including autologous and allogenic embryonic, fetal and adult somatic cells from neural, adipose and mesenchymal tissue. In the present report, we describe a simple protocol to obtain an enriched culture of adult stem cells organized in neurospheres from two post-natal tissues: skin and adipose tissue. METHODS: Adult stem cells isolated from skin and adipose tissue derived from the same adult donor were amplified under varying conditions related to the coating of the chamber slide and the presence of serum and/or growth factors, such as with EGF and FGF2. Neurospheres were then expanded and evaluated in terms of proliferation and gene expression. RESULTS: Adipose and skin derived neurospheres were comparable in size, quantity of cells and genes expressed. Cells from both types of tissue grew optimally without slide coating, in the presence of serum and with the combined addition of FGF2 and EGF. DISCUSSION: We describe a method for isolating and improving a population of multipotent adult precursor cells from the two most accessible adult tissue sources: skin and adipose tissue. This autologous adult stem cell population could be used for cell replacement or cell therapies.
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Papers by Luca Lancerotto