mechanical-controlled-prp-injections-patients-affected-androgenetic

Mechanical and Controlled PRP Injections in Patients Affected by Androgenetic Alopecia

23 patients (18 male and 5 female) aged 21-70 years who displayed male pattern hair loss (MPHL) in Stage 1 to Stage 5 as determined by the ...

University of Rome Tor Vergata

There is considerable attention regarding the role of receptor signaling and downstream-regulated mediators in the homeostasis of adipocytes, but less information is available concerning adipose-derived stem cell (ASC) biology. Recent studies revealed that the pathways regulating ASC differentiation involve the activity of receptor tyrosine kinases (RTKs), including fibroblast growth factor, vascular endothelial growth factor, ErbB receptors and the downstream-regulated serine/threonine protein kinase B (Akt) and phosphatase and tensin homolog (PTEN) activity. RTKs are cell surface receptors that represent key regulators of cellular homeostasis but also play a critical role in the progression of cancer. Many of the metabolic effects and other consequences of activated RTKs are mediated by the modulation of Akt and extracellular signal-regulated protein kinases 1 (Erk-1) signaling. Akt activity sustains survival and the adipogenic differentiation of ASCs, whereas Erk-1 appears downregulated. The inhibition of FGFR-1, EGFR and ErbB2 reduced proliferation, but only FGFR-1 inihibition reduced Akt activity and adipogenesis. Adipogenesis and neovascularization are also chronologically and spatially coupled processes and RTK activation and downstream targets are also involved in ASC-mediated angiogenesis. The potentiality of ASCs and the possibility to modulate specific molecular pathways underlying ASC biological processes and, in particular, those shared with cancer cells, offer new exciting strategies in the field of regenerative medicine.

The biomolecular basis of adipogenic differentiation of adipose-derived stem cells.

Oxidative stress plays a pivotal role in the impaired endothelial function occurring in vascular diseases. Antioxidant strategies induce a clinical advantage in patients with endothelial dysfunction and atherosclerosis and protect from oxidative damage, but the underlying molecular mechanisms have been poorly evaluated. The aim of this study was to analyze the effects and mechanisms of action of antioxidant regimens on endothelial function.

Antioxidant treatment prevents serum deprivation- and TNF-α-induced endothelial dysfunction through the inhibition of NADPH oxidase 4 and the restoration of β-oxidation.

Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery, and preliminary evidence suggests that it might have a beneficial role in hair regrowth. Here, we report the results of a randomized, evaluator-blinded, placebo-controlled, half-head group study to compare, with the aid of computerized trichograms, hair regrowth with PRP versus placebo. The safety and clinical efficacy of autologous PRP injections for pattern hair loss were investigated. PRP, prepared from a small volume of blood, was injected on half of the selected patients' scalps with pattern hair loss. The other half was treated with placebo. Three treatments were administered to each patient at 30-day intervals. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki67 evaluation. Patients were followed for 2 years. Of the 23 patients enrolled, 3 were excluded. At the end of the 3 treatment cycles, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 33.6 hairs in the target area, and a mean increase in total hair density of 45.9 hairs per cm² compared with baseline values. No side effects were noted during treatment. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles 2 weeks after the last PRP treatment compared with baseline value (p < .05). We also observed an increase of Ki67(+) keratinocytes in the epidermis and of hair follicular bulge cells, and a slight increase of small blood vessels around hair follicles in the treated skin compared with baseline (p < .05). Relapse of androgenic alopecia was not evaluated in all patients until 12 months after the last treatment. After 12 months, 4 patients reported progressive hair loss; this was more evident 16 months after the last treatment. Those four patients were re-treated. Our data clearly highlight the positive effects of PRP injections on male pattern hair loss and absence of major side effects. PRP may serve as a safe and effective treatment option against hair loss; more extensive controlled studies are needed.

The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial.

Breast cancer remains the most common tumor in women, and new techniques for post- surgical breast reconstruction have been recently introduced. These new procedures include autologous fat grafting with or without the enrichment with autologous stromal vascular fraction (SVF), platelet-derived growth factors and insulin. The reported improvement of fat graft viability with these techniques likely depends on the presence in the SVF of multipotent resident adipose derived-stem cells (ASCs). The clinical advantage derives from the plasticity of ASCs and their ability to generate new functional adipose tissue and vessels. However, there is an ongoing debate regarding the possible interplay between breast tumor cells and resident or transplanted ASCs for their capacity to locally secrete growth factors. Most of the data in the literature concerning ASCs is derived from in vitro models, whereas the knowledge of ASC behavior in vivo remains scarce. Recent reports concerning SVF/ASC enrichment of fat graft did not describe any significant worsening of prognosis for patients undergoing those procedures. However, further studies and longer follow-ups are needed to specifically define technical procedures and to confirm the safety of procedures of SVF/ASC enrichment during post-surgical breast reconstruction.

Adipose Tissue-Derived Stem Cell Therapy for Post-Surgical Breast Reconstruction--More Light than Shadows.

Type 2 diabetes mellitus (T2DM) is a disease reaching a pandemic proportion in developed countries and a major risk factor for almost all cardiovascular diseases and their adverse clinical manifestations. T2DM leads to several macrovascular and microvascular alterations that influence the progression of cardiovascular diseases. Vascular smooth muscle cells (VSMCs) are fundamental players in macrovascular alterations of T2DM patients. VSMCs display phenotypic and functional alterations that reflect an altered intracellular biomolecular scenario of great vessels of T2DM patients. Hyperglycemia itself and through intraparietal accumulation of advanced glycation-end products (AGEs) activate different pathways, in particular nuclear factor-κB and MAPKs, while insulin and insulin growth-factor receptors (IGFR) are implicated in the activation of Akt and extracellular-signal-regulated kinases (ERK) 1/2. Nuclear factor-κB is also responsible of increased susceptibility of VSMCs to pro-apoptotic stimuli. Down-regulation of insulin growth-factor 1 receptors (IGFR-1R) activity in diabetic vessels also influences negatively miR-133a levels, so increasing apoptotic susceptibility of VSMCs. Alterations of those bimolecular pathways and related genes associate to the prevalence of a synthetic phenotype of VSMCs induces extracellular matrix alterations of great vessels. A better knowledge of those biomolecular pathways and related genes in VSMCs will help to understand the mechanisms leading to macrovascular alterations in T2DM patients and to suggest new targeted therapies.

Molecular Pathways Regulating Macrovascular Pathology and Vascular Smooth Muscle Cells Phenotype in Type 2 Diabetes.

Tissue engineering has emerged at the intersection of numerous disciplines to meet a global clinical need for technologies to promote the regeneration of tissues. Recently, many authors have focused their attention on mesenchymal stem/stromal cells (MSCs) for their capacity to differentiate into many cell lineages. The most widely studied cell types are bone marrow mesenchymal stem cells and adipose-derived stem cells (ASCs), which display similar results. Biomaterials, cells, and growth factors are needed to design a regenerative plastic surgery approach in the treatment of organ and tissue defects, but not all tissues are created equal. The aim of this article is to describe the advances in tissue engineering through the use of ASCs, platelet rich plasma, and biomaterials to enable regeneration of damaged complex tissue. Stem Cells 2017;35:117-134.

Concise Review: The Use of Adipose-Derived Stromal Vascular Fraction Cells and Platelet Rich Plasma in Regenerative Plastic Surgery.

Developing cartilage constructs with injectability, appropriate matrix composition, and persistent cartilaginous phenotype remains an enduring challenge in cartilage repair. The combined use of autologous chondrocyte micrografts and platelet-rich plasma (PRP) is an alternative that opens a new era in this field.

Reconstruction of Alar Nasal Cartilage Defects Using a Tissue Engineering Technique Based on a Combined Use of Autologous Chondrocyte Micrografts and Platelet-rich Plasma: Preliminary Clinical and Instrumental Evaluation.

Platelet rich plasma (PRP) was tested as a potential therapy for androgenetic alopecia (AGA) through two different clinical protocols in which one population (18 participants) received half-head treatment with autologous non-activated PRP (A-PRP) produced by CPunT Preparation System (Biomed Device, Modena, Italy) and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group) received treatment with calcium-activated PRP (AA-PRP) produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System). For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs) and in total hair density (65±  5 hair cm2), whereas negligible improvements in hair count (1.1±  1.4 hairs) and density (1.9 ± 10.2 hair cm2) were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex). Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems.

Hair follicles are known to contain a well-characterized niche for adult stem cells: the bulge, which contains epithelial and melanocytic stem cells. Stem cells in the hair bulge, a clearly demarcated structure within the lower permanent portion of hair follicles, can generate the interfollicular epidermis, hair follicle structures, and sebaceous glands. The bulge epithelial stem cells can also reconstitute in an artificial in vivo system to a new hair follicle.

Stem cells from human hair follicles: first mechanical isolation for immediate autologous clinical use in androgenetic alopecia and hair loss.

Implants made from naturally-derived biomaterials, also called biological meshes or biomeshes, typically derive from decellularized extracellular matrix of either animal or human tissue. Biomeshes have many biomedical applications such as ligament repair, bone and cartilage regeneration and soft tissue replacement. Bovine collagen is one of the most widely used and abundantly available xenogenic materials. In particular, bovine pericardium is widely used as extracellular matrix bioprosthetic tissue. The efficiency of a pericardial mesh to function as scaffold depends on the quality of the decellularization protocol used. Moreover, the biomesh mechanical features are critical for a successful surgical repair process, as they must reproduce the biological properties of the autologous tissue. Different methods of physical, chemical, or enzymatic decellularization exist, but no one has proved to be ideal. Therefore, in the present study, we developed a novel decellularization protocol for a bovine pericardium-derived biomesh. We characterized the biomesh obtained by comparing some ultrastructural, physical and mechanical features to a reference commercial biomesh. Quantification revealed that our novel decellularization process removed about 90% of the native pericardial DNA. Microscopic and ultrastructural analysis documented the maintenance of the physiological structure of the pericardial collagen. Moreover, mechanical tests showed that both the extension and resilience of the new biomesh were statistically higher than the commercial control ones. The results presented in this study demonstrate that our protocol is promising in preparing high quality bovine pericardial biomeshes, encouraging further studies to validate its use in tissue engineering and regenerative medicine protocols.

Characterization of a new decellularized bovine pericardial biological mesh: Structural and mechanical properties.

Recently, a new fat grafting technique termed 'nanofat grafting' was proposed which improved tissue repair by the stem cells contained in the stromal vascular fraction (SVF) of nanofat. Here, we reported the clinical outcomes of different nanofat procedures in the treatment of scars in relation with SVF cell yield.

Article	Year
The biomolecular basis of adipogenic differentiation of adipose-derived stem cells. International journal of molecular sciences\| PubMed ID: 24743893	2014
Antioxidant treatment prevents serum deprivation- and TNF-α-induced endothelial dysfunction through the inhibition of NADPH oxidase 4 and the restoration of β-oxidation. Journal of vascular research\| PubMed ID: 25401479	2014
The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial. Stem cells translational medicine\| PubMed ID: 26400925	2015
Adipose Tissue-Derived Stem Cell Therapy for Post-Surgical Breast Reconstruction--More Light than Shadows. Advances in clinical and experimental medicine : official organ Wroclaw Medical University\| PubMed ID: 26467147	2015
Molecular Pathways Regulating Macrovascular Pathology and Vascular Smooth Muscle Cells Phenotype in Type 2 Diabetes. International journal of molecular sciences\| PubMed ID: 26473856	2015
Concise Review: The Use of Adipose-Derived Stromal Vascular Fraction Cells and Platelet Rich Plasma in Regenerative Plastic Surgery. Stem cells (Dayton, Ohio)\| PubMed ID: 27641055	2017
Reconstruction of Alar Nasal Cartilage Defects Using a Tissue Engineering Technique Based on a Combined Use of Autologous Chondrocyte Micrografts and Platelet-rich Plasma: Preliminary Clinic... Plastic and reconstructive surgery. Global open\| PubMed ID: 27826462	2016
Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems. International journal of molecular sciences\| PubMed ID: 28216604	2017
Stem cells from human hair follicles: first mechanical isolation for immediate autologous clinical use in androgenetic alopecia and hair loss. Stem cell investigation\| PubMed ID: 28725654	2017
Characterization of a new decellularized bovine pericardial biological mesh: Structural and mechanical properties. Journal of the mechanical behavior of biomedical materials\| PubMed ID: 29223730	2018
Comparing different nanofat procedures on scars: role of the stromal vascular fraction and its clinical implications. Regenerative medicine\| PubMed ID: 29236575	2017

Alessandra Bielli

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