Rejuvenation of human mesenchymal stem cells using a nonintegrative and conditionally removable Sendai virus vector.

Human mesenchymal stem cells (hMSCs) with extended lifespan and differentiation potential that can recapitulate in vivo characteristics could significantly contribute to basic research, drug development, and cell therapy. Specifically, they could ensure a stable supply of specific cellular resources, and possibly extracellular vesicles. Here, we established a technology for extending the lifespan while maintaining differentiation potential, termed "rejuvenation," of hMSCs (rej-hMSCs) using nonintegrative and conditionally removable temperature-sensitive Sendai virus (SeV) vectors. Various immortalizing factors (i.e., Bmi-1, hTERT, SV40T, and/or HPV E6/E7) were first introduced by the SeV vector into the cells. A combination of three SeVs with Bmi-1, hTERT, or SV40T conferred markedly improved cell proliferation and cloning ability while maintaining differentiation potential and a normal karyotype. An extended lifespan was also demonstrated in other cell types. The rejuvenation of long-passaged or aged hMSCs was also confirmed. SeV vectors were rapidly removed as a function of cell doubling by increasing the temperature from 35 °C to 37 °C or higher, while proliferative ability was maintained. Following FACS sorting, the complete removal of SeV vectors was confirmed by qPCR analyses. Therefore, our cell rejuvenation technology could contribute to research and clinical applications by enabling the supply of modified cells without damaging host chromosomes.

Full Face Application of Topical Platelet Extract for Skin Rejuventation in Monozygotic Twins.

Two monozygotic twins (Fitzpatrick skin type II 56-year-old women) with significant photoaging and mild to moderate global fine lines based on the modified Griffiths 10-point scale were enrolled in the study. The past medical etymology and laboratory evaluation were unremarkable. Each subject followed a standardized skin care regimen with topical platelet renewosomesTM (human platelet extract [HPE]) daily for a 12-week duration.1-4 In order to evaluate aesthetic outcomes/changes subjectively, three blinded board-certified plastic surgeons (Yael Halaas, K. Kay Durairaj, and Michael Somenek) compared photographs between baseline and 12-week follow-up (Figure 1). This evaluation was completed using the Global Aesthetic Improvement Scale (GAIS) and the modified Griffiths 10-point scale.5,6.

Noninvasive high-intensity focused ultrasound for skin brightening efficacy using a topical agent containing glutathione and hyaluronic acid.

BACKGROUND: High-intensity focused ultrasound (HIFU) is well-documented for skin rejuvenation, lifting, and tightening. However, its synergistic effects with topical agents, enhanced by HIFU-induced vibration and heat, remain underexplored. OBJECTIVE: To evaluate clinical and photographic outcomes of HIFU combined with a topical agent versus the topical agent alone. METHOD: This non-randomized controlled trial involved 20 female volunteers (ages 30-55) divided into two groups. Group A (n = 10) received two HIFU sessions combined with a topical agent containing glutathione and hyaluronic acid. Group B (n = 10) received the topical agent alone. Outcomes were assessed using digital photography, patient satisfaction surveys, and the A-One Smart™ system for fine wrinkles, hyperpigmentation, and hydration. Skin brightening was evaluated with the Global Esthetic Improvement Scale (GAIS). RESULTS: Group A showed significant reductions in fine wrinkles (6.25 ± 2.00 mm to 3.10 ± 1.62 mm), improved hyperpigmentation (3.50 ± 0.80 to 2.10 ± 1.05), and increased hydration (28 ± 10 to 55 ± 11) (all p < 0.05). Over two-thirds of Group A reported significant improvements, with no complications. Group B showed minimal, non-significant changes (p > 0.05), with only 30% reporting noticeable improvements. CONCLUSION: Combining HIFU with a topical agent significantly enhances skin quality and brightness without adverse effects.

EphA4 Targeting Peptide-Conjugated Extracellular Vesicles Rejuvenates Adult Neural Stem Cells and Exerts Therapeutic Benefits in Aging Rats.

Aging and various neurodegenerative diseases cause significant reduction in adult neurogenesis and simultaneous increase in quiescent neural stem cells (NSCs), which impact the brain's regenerative capabilities. To deal with this challenging issue, current treatments involve stem cell transplants or prevention of neurodegeneration; however, the efficacy or success of this process remains limited. Therefore, extensive and focused investigation is highly demanding to overcome this challenging task. Here, we have designed an efficient peptide-based EphA4 receptor-targeted ligand through an in silico approach. Further, this strategy involves chemical conjugation of the peptide with adipose tissue stem cell-derived EV (Exo-pep-11). Interestingly, our newly designed engineered EV, Exo-pep-11, targets NSC through EphA4 receptors, which offers promising therapeutic advantages by stimulating NSC proliferation and subsequent differentiation. Our result demonstrates that NSC successfully internalized Exo-pep-11 in both in vitro culture conditions as well as in the in vivo aging rats. We found that the uptake of Exo-pep-11 decreased by ∼2.3-fold when NSC was treated with EphA4 antibody before Exo-pep-11 incubation, which confirms the receptor-specific uptake of Exo-pep-11. Exo-pep-11 treatment also increases NSC proliferation by ∼1.9-fold and also shows ∼1.6- and ∼2.4-fold increase in expressions of Nestin and ID1, respectively. Exo-pep-11 also has the potential to increase neurogenesis in aging rats, which is confirmed by ∼1.6- and ∼1.5-fold increases in expressions of TH and Tuj1, respectively, in rat olfactory bulb. Overall, our findings highlight the potential role of Exo-pep-11 for prospective applications in combating age-related declines in NSC activity and neurogenesis.

Rejuvenation of aged oocyte through exposure to young follicular microenvironment.

Reproductive aging is a major cause of fertility decline, attributed to decreased oocyte quantity and developmental potential. A possible cause is aging of the surrounding follicular somatic cells that support oocyte growth and development by providing nutrients and regulatory factors. Here, by creating chimeric follicles, whereby an oocyte from one follicle was transplanted into and cultured within another follicle whose native oocyte was removed, we show that young oocytes cultured in aged follicles exhibited impeded meiotic maturation and developmental potential, whereas aged oocytes cultured within young follicles were significantly improved in rates of maturation, blastocyst formation and live birth after in vitro fertilization and embryo implantation. This rejuvenation of aged oocytes was associated with enhanced interaction with somatic cells, transcriptomic and metabolomic remodeling, improved mitochondrial function and higher fidelity of meiotic chromosome segregation. These findings provide the basis for a future follicular somatic cell-based therapy to treat female infertility.

Pharmacologic and Other Noninvasive Treatments of the Aging Face: A Review of the Current Evidence.

SUMMARY: Aging of the face is the result of the interrelation of three-dimensional changes occurring over time among the 5 different layers of the face and its associated structures. Knowledge regarding the causes of these changes and identification of new key anatomic structures have helped elucidate one of the most complex areas of the human body. This has resulted in the introduction of pharmacologic agents to help stop, mitigate, or counteract signs of aging and restore the youthful appearance of the face. The authors performed a systematic search of the literature to review the current highest-level evidence of facial antiaging pharmacologic agents. Pharmacologic and minimally invasive antiaging treatments can target different components of facial aging and continue to evolve. With continuous research efforts, traditional treatments, such as botulinum toxin type A, injectable fillers, and chemical peels, are emerging in newer, more effective formulations, with longer lasting clinical results. However, for soft-tissue descent and facial volume loss, surgery remains the standard treatment. An adequate understanding of the three-dimensional process of facial aging over time (the fourth dimension), facial anatomy, and the pharmacologic properties of antiaging/rejuvenation agents are the sine qua non of facial antiaging treatment. The specific modality should be tailored to patient characteristics, preferences, and goals.

A Personalized Protocol for Facial Rejuvenation Using Two Soft Hyaluronic Acid Fillers With High Cohesivity.

Minimally invasive injectable dermal fillers are one of the most commonly used aesthetic treatments for facial soft tissue restoration. Different formulations may be used simultaneously to target multiple areas of concern. Due to differences in their rheological properties that directly impact the recommended injection technique and overall result, the formulations in the Aliaxin® line are each designed to target different soft facial tissues. This case series addresses two potential treatment approaches and a combination approach specifically developed to achieve harmony and promote a full but soft facial appearance. To reach this goal, we used two different formulations: Aliaxin® Shape and Restore (ASR) and Aliaxin® Global Performance (AGP). Four patients, 35-55 years received treatments with ASR, AGP, or both products. Utilizing the two protocols simultaneously achieved targeted support, lift, and volume, along with effective full facial softening and an authentic aesthetic outcome.

The cell rejuvenation atlas: leveraging network biology to identify master regulators of rejuvenation strategies.

Current rejuvenation strategies, which range from calorie restriction to in vivo partial reprogramming, only improve a few specific cellular processes. In addition, the molecular mechanisms underlying these approaches are largely unknown, which hinders the design of more holistic cellular rejuvenation strategies. To address this issue, we developed SINGULAR (Single-cell RNA-seq Investigation of Rejuvenation Agents and Longevity), a cell rejuvenation atlas that provides a unified system biology analysis of diverse rejuvenation strategies across multiple organs at single-cell resolution. In particular, we leverage network biology approaches to characterize and compare the effects of each strategy at the level of intracellular signaling, cell-cell communication, and transcriptional regulation. As a result, we identified master regulators orchestrating the rejuvenation response and propose that targeting a combination of them leads to a more holistic improvement of age-dysregulated cellular processes. Thus, the interactive database accompanying SINGULAR is expected to facilitate the future design of synthetic rejuvenation interventions.

Rejuvenation of the reconstitution potential and reversal of myeloid bias of aged HSCs upon pH treatment.

Aged hematopoietic stem cells (HSCs) show reduced reconstitution potential, limiting their use in transplantation settings in the clinic. We demonstrate here that exposure of aged HSCs ex vivo to a pH of 6.9 instead of the commonly used pH of 7.4 results in enhanced HSCs potential that is consistent with rejuvenation, including attenuation of the myeloid bias of aged HSC and restoration of a youthful frequency of epigenetic polarity. Rejuvenation of aged HSCs by pH 6.9 is, at least in part, due to alterations in the polyamine/methionine pathway within pH 6.9 HSCs, and consequently, attenuation of the production of spermidine also attenuated aging of HSCs. Exposure of aged HSCs to pH 6.9, or pharmacological targeting of the polyamine pathway, might thus extend the use of HSCs from aged donors for therapeutic applications.

Evaluation of the photothermal effects of the subdermal high-power laser in the skin of an experimental rat model.

The aim of the present study was to evaluate the photothermal effects of a subdermal high-power diode laser at a wavelength (λ) of 1470 nm in the skin of rats. Twenty male Wistar rats were used, divided into 2 groups: placebo laser (PL) and active laser (AL). A high-power diode laser equipment was applied to 5 subdermal vectors on the animal's back region. The results demonstrated that active laser animals showed a better arrangement of collagen fiber bands, an increase in the thickness of the dermis and the number of vessels. Furthermore, animals treated with active laser showed an increased immunoexpression of TGF-ß and VEGF compared to the placebo. The present work demonstrated that the subdermal high-power diode laser increases the vascularization and the expression of factors that enhance skin regeneration and may be promising resource in the esthetic and dermatology clinical treatment of skin rejuvenation.

Real-World Experience Using a Multi-Modality System using Intense Pulsed Light, Radiofrequency Microneedling, High-Intensity Focused Ultrasound, or Thermal Radiofrequency, 808, HIFU for Skin Rejuvenation Treatment.

BACKGROUND: Medical aesthetic procedures for facial rejuvenation with laser and energy-based devices (EBDs) are rapidly increasing. The following cases highlight real-life experience using a multi-modality system with various handpieces that combine intense pulsed light (IPL), laser hair removal (808 diode), high-intensity focused ultrasound (HIFU), radiofrequency microneedling (RFM), and thermal radiofrequency (RF) for antiaging and rejuvenation treatment. Laser and RFM treatments may improve skin conditions by inducing cutaneous changes that remodel the skin matrix. METHODS: Six physicians who treat patients for skin rejuvenation reported on clinical cases from their practice using a multi-modality system with various handpieces. RESULTS: During the meeting, the advisors discussed 15 cases and agreed to select seven patients with different ages and skin phototypes receiving various treatments for photodamage of the face, neck, and décolleté. The advisors discussed why they selected the case, previous treatment, type of treatment, results, and clinical pearls. CONCLUSION: Sharing best practices in medical aesthetics using combination treatments on a single multi-modality energy-based device such as laser and MRF for facial, neck, and chest skin may support healthcare providers treating patients for skin rejuvenation to improve clinical outcomes.

Effect of Topical Human Platelet Extract (HPE) for Facial Skin Rejuvenation: A Histological Study of Collagen and Elastin.

BACKGROUND: Regenerative aesthetics has garnered significant attention. In this toolkit, exosomes are small extracellular vesicles derived from various sources such as platelets. OBJECTIVE: To characterize the cosmetic effect and tolerability of topical human platelet-derived extract (HPE), Intense Serum (Rion Aesthetics, Inc., Rochester, MN), on facial skin rejuvenation after 12 weeks of twice daily use without any confounding aesthetic procedures. MATERIALS AND METHODS: This prospective, single-arm, non-randomized, evaluator-blinded clinical study evaluated subjects at baseline and 12 weeks using participant questionnaires and photo-documentation with Canfield VISIA-CR 3D PRIMOS. The histological evaluation included Masson's Trichrome for collagen and Verhoeff-Van Gieson staining for elastin. Electron microscopy characterized collagen bundle thickness. RESULTS: Fifty-six participants (mean age: 54 years old) were enrolled. Following topical HPE use, 87.3% of subjects reported improvement in facial skin aging including sustained pigment reduction and improvement in luminosity and color evenness at 12 weeks (P≤0.001). Histology revealed a significant increase in collagen fibril thickness at 12 weeks (P≤0.0001). No serious adverse effects. CONCLUSION: This study demonstrates improvement in facial skin health after topical HPE use, supported by collagen and elastin formation in the dermis. The product is well-tolerated, and participants were satisfied with the overall cosmetic outcome. J Drugs Dermatol. 2024;23(9):735-740. doi:10.36849/JDD.8162.

A Clinical Histology Study Evaluating the Biostimulatory Activity Longevity of Injectable Poly-L-Lactic Acid for Facial Rejuvenation.

BACKGROUND: Poly-L-lactic acid (PLLA) is an injectable filler used for restoring facial fat volume loss that improves skin quality. OBJECTIVE: To evaluate the histological changes underlying the observed improvement in skin quality after repeated PLLA injections. METHODS: Ten healthy women were enrolled in this randomized, placebo-controlled, single-center study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections, into both sides of the face. Follow-up visits were at week 18 after the last treatment. Assessments included live ratings, patient questionnaires, three-dimensional microtopography imaging analysis, and histological analysis from biopsies taken before and after PLLA treatment. RESULTS: At the 18-week follow-up, there was a significant improvement in investigator- and subject-rated global aesthetic improvement (GAIS) scores, as well as a decrease in wrinkle severity in PLLA-treated but not placebo-treated patients. Skin quality parameters of erythema, pore size, and roughness were significantly improved from baseline and compared with placebo at the 18-week follow-up as assessed by microtopographic analysis and investigator ratings. Histologic analysis revealed increased tissue remodeling and angiogenesis in PLLA-treated tissues at the 18-week follow-up and decreased elastin fragmentation compared with baseline. No treatment-related adverse events occurred. CONCLUSION: Repeated PLLA treatments may improve skin quality through tissue remodeling and neovascularization. J Drugs Dermatol. 2024;23(9):729-734. doi:10.36849/JDD.8057.

INDIVIDUAL ARTICLE: Real-World Patient Cases Using Triple Lipid-Containing Cream for Cutaneous Healing Post Laser or Microneedling Radiofrequency Treatment.

Lipids play an essential role in skin barrier health. With age, there is a natural reduction of physiological lipids such as fatty acids, ceramides, and cholesterol. The triple lipid restore cream is a moisturizer that contains an optimized lipid ratio for aging skin. The cream contains a 2:4:2 ratio of ceramides, cholesterol, and fatty acids that have been shown to best support aging skin. The triple lipid restore cream has been used in combination with energy-based procedures, to provide patients with comprehensive integrated skincare regimens. With limited clinical data and guidelines available in regenerative medicine, real-world cases serve as an invaluable guide for patients and dermatologists in navigating rejuvenation treatment plans. J Drugs Dermatol. 2024;23:9(Suppl 1):s3-14.

The Safe and Effective Profile of Using the 1340 nm Wavelength in Conjunction with Other Therapeutic Modalities for Skin Rejuvenation. A Case Series.

Objective: This study provided clinical findings supporting the use of combination techniques/products and Nd:YAP 1340 nm fractional laser therapy, for soft-tissue augmentation in light- and darker-skin phototypes. Background: The face's aging process is complex and involves skin alterations, connective tissues, bone, and fat layers of the face. Methods: A total of 17 female patients were treated for wrinkles and for scars with the use of Nd:YAP 1340 nm fractional laser combined with other cosmetic therapies. The mean of 4.6(±1.9) laser treatment sessions every 1 month were performed. The combined therapy was administered every 3 months during the total course of the laser treatments. Results: The total mean improvement was 3.64(±0.49). Clinical images showed a visible aesthetic improvement. No adverse events have been reported. Conclusion: The combination therapies used have shown promise in maintaining safety and tolerability while improving patient results for the management of skin aging.

ImAge quantitates aging and rejuvenation.

For efficient, cost-effective and personalized healthcare, biomarkers that capture aspects of functional, biological aging, thus predicting disease risk and lifespan more accurately and reliably than chronological age, are essential. We developed an imaging-based chromatin and epigenetic age (ImAge) that captures intrinsic age-related trajectories of the spatial organization of chromatin and epigenetic marks in single nuclei, in mice. We show that such trajectories readily emerge as principal changes in each individual dataset without regression on chronological age, and that ImAge can be computed using several epigenetic marks and DNA labeling. We find that interventions known to affect biological aging induce corresponding effects on ImAge, including increased ImAge upon chemotherapy treatment and decreased ImAge upon caloric restriction and partial reprogramming by transient OSKM expression in liver and skeletal muscle. Further, ImAge readouts from chronologically identical mice inversely correlated with their locomotor activity, suggesting that ImAge may capture elements of biological and functional age. In sum, we developed ImAge, an imaging-based biomarker of aging with single-cell resolution rooted in the analysis of spatial organization of epigenetic marks.

Advancements in laser technologies for skin rejuvenation: A comprehensive review of efficacy and safety.

INTRODUCTION: Laser technology has fundamentally transformed the landscape of dermatology, offering nuanced solutions for skin rejuvenation and resurfacing. This paper aims to explore the spectrum of laser technologies, from ablative to non-ablative and fractional lasers, their mechanisms, benefits, and tailored applications for diverse skin conditions. As we delve into the intricacies of each technology, we also consider the scientific advancements that have made these treatments safer and more effective, promising a new horizon in skin rejuvenation. OBJECTIVE: This comprehensive analysis seeks to evaluate recent advancements in laser technology for skin rejuvenation, focusing on efficacy, safety, and patient satisfaction. METHODS: The selection criteria for studies in this publication focused on recent, peer-reviewed articles from the last 20 years, emphasizing advancements in laser technologies for skin rejuvenation. Our comprehensive review involved searches in PubMed, Cochrane, Scopus and Google Scholar using keywords like "skin rejuvenation," "laser technology," "efficacy," "safety," and "dermatology." This approach focused on inclusion of recent research and perspectives on the efficacy and safety of laser treatments in the field of dermatology. RESULTS: Our literature review reveals advancements in laser skin resurfacing technologies, notably fractional lasers for minimal downtime rejuvenation, ablative lasers for precise tissue vaporization, and non-ablative lasers for coagulation effect promoting collagen with reduced recovery. Hybrid and picosecond lasers are highlighted for their versatility and effectiveness in addressing a wide array of skin concerns. The findings also emphasize the development of safer treatment protocols for ethnic skin, significantly reducing risks like hyperpigmentation and scarring, thus broadening the scope of effective dermatological solutions. CONCLUSION: This extensive review of advancements in laser technologies for skin rejuvenation underscores a remarkable evolution in dermatological treatments, offering an expansive overview of the efficacy, safety, and patient satisfaction associated with these interventions. Furthermore, the exploration of combination treatments and laser-assisted drug delivery represents a frontier in dermatological practice, offering synergistic effects that could amplify the therapeutic benefits of laser treatments.

INDIVIDUAL ARTICLE: Skincare in Skin of Color: A Comprehensive Approach to Preprocedure, Intraprocedure, and Postprocedure.

Hyperpigmentation, uneven skin tone, textural changes, and dull skin are common cosmetic concerns in skin of color. Other signs of aging, including fine lines, deeper wrinkles, and skin laxity, also occur but may present in later decades. In-office procedures such as laser treatments, energy devices, toxins, fillers, and chemical peels are useful options for addressing the most common cosmetic concerns in skin of color patients. Skincare can play an important role in improving cosmetic outcomes when used in conjunction with in-office procedures. With the availability of these approaches, clinicians can now integrate in-office procedures with skincare strategies to offer patients with skin of color a comprehensive treatment plan that meets their needs. J Drugs Dermatol. 2024;23:8(Suppl 1):s5-10.

Rejuvenation of BMSCs senescence by pharmacological enhancement of TFEB-mediated autophagy alleviates aged-related bone loss and extends lifespan in middle aged mice.

Bone marrow stromal/stem cells (BMSCs) are generally considered as common progenitors for both osteoblasts and adipocytes in the bone marrow, but show preferential differentiation into adipocytes rather than osteoblasts under aging, thus leading to senile osteoporosis. Accumulated evidences indicate that rejuvenation of BMSCs by autophagic enhancement delays bone aging. Here we synthetized and demonstrated a novel autophagy activator, CXM102 that could induce autophagy in aged BMSCs, resulting in rejuvenation and preferential differentiation into osteoblasts of BMSCs. Furthermore, CXM102 significantly stimulated bone anabolism, reduced marrow adipocytes, and delayed bone loss in middle-age male mice. Mechanistically, CXM102 promoted transcription factor EB (TFEB) nuclear translocation and favored osteoblasts formation both in vitro and in vivo. Moreover, CXM102 decreased serum levels of inflammation and reduced organ fibrosis, leading to a prolonger lifespan in male mice. Our results indicated that CXM102 could be used as an autophagy inducer to rejuvenate BMSCs and shed new lights on strategies for senile osteoporosis and healthyspan improvement.