Autologous Adipose-derived Stem Cells Research Articles

Supplementation with autologous adipose stem cell-derived mitochondria can be a safe and promising strategy for improving oocyte quality.

In our previous study, we confirmed that the supplementation of vitrified-warmed murine oocytes with autologous adipose stem cell (ASC)-derived mitochondria during intracytoplasmic sperm injection enhances post-fertilization developmental competence in mice. To ensure the safety of this technology, we conducted a thorough study in mice to investigate the potential presence of specific malformations in offspring developed from this approach. A transgenerational comparative analysis was conducted on founder mice from embryos that developed after mitochondrial supplementation, and two subsequent generations. Reproductive performance, body growth rate, histopathological parameters, hematological parameters, daily activity patterns, and daily body temperature changes in male and female mice across these three generations were assessed in comparison to wild-type mice of the same age. Both male and female animals in all three generations showed comparable reproductive performance to the control group. Additionally, body growth rate by the age of 8weeks were found to be comparable to controls across all three generations. Notably, no significant histopathological abnormalities were detected in vital organs, including the brain, heart, liver, kidneys, lungs, ovaries, and testes, in any individuals from the studied cohorts. The blood parameters were consistent with the control data. The continuous monitoring of activity and body temperature changes (both day and night) over a 1-week period revealed a pattern closely resembling that observed in the control animals. Injection of ASC-mitochondria into oocytes may be a promising technique to support developmental potential without causing adverse epigenetic events in the offspring in mice. However, before considering clinical application, additional safety screening using larger animals or non-human primates is essential.

Extremely low frequency–electromagnetic fields promote chondrogenic differentiation of adipose-derived mesenchymal stem cells through a conventional genetic program

Progressive cartilage deterioration leads to chronic inflammation and loss of joint function, causing osteoarthritis (OA) and joint disease. Although symptoms vary among individuals, the disease can cause severe pain and permanent disability, and effective therapies are urgently needed. Human Adipose-Derived Stem Cells (ADSCs) may differentiate into chondrocytes and are promising for treating OA. Moreover, recent studies indicate that electromagnetic fields (EMFs) could positively affect the chondrogenic differentiation potential of ADSCs. In this work, we investigated the impact of EMFs with frequencies of 35 Hertz and 58 Hertz, referred to as extremely low frequency-EMFs (ELF–EMFs), on the chondrogenesis of ADSCs, cultured in both monolayer and 3D cell micromasses. ADSC cultures were daily stimulated for 36 min with ELF–EMFs or left unstimulated, and the progression of the differentiation process was evaluated by morphological analysis, extracellular matrix deposition, and gene expression profiling of chondrogenic markers. In both culturing conditions, stimulation with ELF–EMFs did not compromise cell viability but accelerated chondrogenesis by enhancing the secretion and deposition of extracellular matrix components at earlier time points in comparison to unstimulated cells. This study showed that, in an appropriate chondrogenic microenvironment, ELF–EMFs enhance chondrogenic differentiation and may be an important tool for supporting and accelerating the treatment of OA through autologous adipose stem cell therapy.

The Healing and Aging-related Properties of Adipose Tissue Fragments Obtained through the Guided SEFFI Procedure’s Mechanical Fragmentation are Facilitated by the Exosomes Present in the Final Injection

The Injection of autologous Adipose-Derived Stem Cells (ADSCs) and Stromal Vascular Fraction (SVF) into dermal and subdermal layers can improve skin volume and rejuvenation. The SEFFI (Superficial Enhanced Fluid Fat Injection) technique, which involves minimal manipulation of autologous microfragmented adipose tissue, was utilized for harvesting and re-injection, using the SEFFILLER™ disposable medical device. Mechanical fragmentation of adipose tissue is a well-established surgical technique that stimulates tissue regeneration, filler, and biological activity. The study evaluated the biological properties (regenerative and anti-aging) of different harvest and processing fat graft methods among which the fragmented adipose tissue, specifically focusing on the presence of exosomes. Exosomes, nanometer-sized vesicles produced by cells for cellular communication, were found to contain miRNAs with anti-inflammatory, regenerative, and vascular content. The products’ contained exosomes were confirmed in the study through electron microscopy, Western Blotting, gene expression, and sequencing of miRNA content.

Tissue-engineered bone construct promotes early osseointegration of implants with low primary stability in oversized osteotomy

ObjectivesTo evaluate the histological parameters and bone mechanical properties around implants with low primary stability (PS) in grafted bone substitutes within an oversized osteotomy.Materials and methodsAn oversized osteotomy penetrating the double cortical bone layers was made on both femora of 24 New Zealand white rabbits. Bilaterally in the femur of all animals, 48 implants were installed, subdivided into four groups, corresponding to four prepared tissue-engineering bone complexes (TEBCs), which were placed between the implant surface and native bone wall: A: tricalcium phosphate β (TCP-β); B: autologous adipose derived-stem cells with TCP-β (ASCs/TCP-β); C: ASCs transfected with the enhanced-GFP gene with TCP-β (EGFP-ASCs/TCP-β); D: ASCs transfected with the BMP-2 gene with TCP-β (BMP2-ASCs/TCP-β). Trichrome fluorescent labeling was conducted. Animals were sacrificed after eight weeks. The trichromatic fluorescent labeling (%TFL), area of new bone (%NB), residual material (%RM), bone-implant contact (%BIC), and the removal torque force (RTF, N/cm) were assessed.ResultsASCs were successfully isolated from adipose tissue, and the primary ASCs were induced into osteogenic, chondrogenic, and adipogenic differentiation. The BMP-2 overexpression of ASCs sustained for ten days and greatly enhanced the expression of osteopontin (OPN). At eight weeks post-implantation, increased %NB and RTF were found in all groups. The most significant value of %TFL, %BIC and lowest %RM was detected in group D.ConclusionThe low PS implants osseointegrate with considerable new bone in grafted TEBCs within an oversized osteotomy. Applying BMP-2 overexpressing ASCs-based TEBC promoted earlier osseointegration and more solid bone mechanical properties on low PS implants. Bone graft offers a wedging effect for the implant with low PS at placement and promotes osteogenesis on their surface in the healing period.

Metformin and adipose-derived stem cell combination therapy alleviates radiation-induced skin fibrosis in mice

BackgroundRadiation therapy often leads to late radiation-induced skin fibrosis (RISF), causing movement impairment and discomfort. We conducted a comprehensive study to assess the effectiveness of metformin and adipose-derived stem cells (ASCs), whether autologous or allogeneic, individually or in combination therapy, in mitigating RISF.MethodsUsing a female C57BL/6J mouse model subjected to hind limb irradiation as a representative RISF model, we evaluated metformin, ASCs, or their combination in two contexts: prophylactic (started on day 1 post-irradiation) and therapeutic (initiated on day 14 post-irradiation, coinciding with fibrosis symptoms). We measured limb movement, examined skin histology, and analyzed gene expression to assess treatment efficacy.ResultsProphylactic metformin and ASCs, whether autologous or allogeneic, effectively prevented late fibrosis, with metformin showing promising results. However, combination therapy did not provide additional benefits when used prophylactically. Autologous ASCs, alone or with metformin, proved most effective against late-stage RISF. Prophylactic intervention outperformed late therapy for mitigating radiation skin damage. Co-culture studies revealed that ASCs and metformin downregulated inflammation and fibrotic gene expression in both mouse and human fibroblasts.ConclusionsOur study suggests metformin's potential as a prophylactic measure to prevent RISF, and the combination of ASCs and metformin holds promise for late-stage RISF treatment. These findings have clinical implications for improving the quality of life for those affected by radiation-induced skin fibrosis.

Autologous fat grafting and adipose-derived stem cells therapy for acute burns and burn-related scar: A systematic review.

The objective of this study was to analyze all available research on the application of autologous fat grafting (AFG) and adipose-derived stem cells (ADSC) to present evidence-based recommendations, particularly in the clinical treatment of acute burns and burn-related scars. We conducted a systematic search of PubMed, COCHRANE, and EMBASE, as well as a manual search of previous reviews' reference lists up. The risk of bias (RoB) was assessed using RoB 2.0 and ROBINS-I, where appropriate. Six eligible studies were selected (2 randomized clinical trials [RCT], 1 retrospective cohort, and 3 experimental studies) with subjects ranging from 3 to 100. Only one study evaluated the use of AFG for acute burns. Improvements in wound healing, vascularization, scar characteristics, and tissue architecture were generally observed in some studies, supported by molecular markers, while one study reported nonsignificant results. Subjective patient satisfaction was reported to have improved. Functional outcomes improvement in the treated regions was minimal. However, study heterogeneity arose mainly from treatment protocols. Cautious results interpretation due to potential bias, especially in selection and confounding domains, and limited clinical trials are important to note. More studies are needed to evaluate. AFG and ADSC hold potential as valuable treatment options for burn-related scars, supported by a body of evidence, but further well-designed RCT are needed. The efficacy of acute burn settings is yet to be further evaluated since evidence is limited.

Investigation of Expanded Human Adipose-derived Stem Cell Dosage and Timing for Improved Defecation Function.

Although certain treatment options exist for intestinal incontinence, none are curative. Adipose-derived stem cells (ADSCs) have emerged as promising therapeutic agents, but most preclinical studies of their effectiveness for anal function have used autologous or allogeneic ADSCs. In this study, the effectiveness, timing of administration, and required dosage of human ADSCs were investigated for clinical application. A 10-mm balloon catheter was used to induce anal sphincter injury in immunodeficient mice in the following experimental groups (n=4 per group): ADSC (injected ADSCs after injury), PBS (injected phosphate-buffered saline after injury), and control (uninjured). The effects of different timing (immediately after injection and 30 days following injury) and number of human ADSCs administered was compared among groups based on defecation status and pathological evaluation. In terms of defecation status, groups receiving ≥1×104 human ADSCs after injection showed improvement. Pathological images showed that compared to the PBS group, the thinnest part of the sphincter was thicker for animals that received ≥1×104 human ADSCs, and fibrosis of the sphincter was notable in those treated with 1×103 human ADSCs or PBS. Furthermore, defecation status was improved by administration of human ADSCs, not only immediately after injury, but also at 30 days following injury. Human ADSC administration in a mouse model of anal sphincter injury was effective. Injection of ≥1×104 human ADSCs was the amount necessary to improve defecation status, an effect detected in both the acute and chronic phases.

Functional recovery of a 41-year-old quadriplegic spinal cord injury patient following multiple intravenous infusions of autologous adipose-derived mesenchymal stem cells: a case report

Spinal cord injury (SCI) is a debilitating disease with clinical manifestations ranging from incomplete neurological deficits affecting sensory and motor functions to complete paralysis. Recent advancements in stem cell research have elucidated the therapeutic potential of mesenchymal stem cells (MSCs) for the treatment of patients with SCI. Here, we present a case of a 41-year-old quadriplegic male individual who experienced a traumatic C-5 incomplete SCI, after slipping off a boat in Florida Keys on August 4, 2017. He was diagnosed with C5–C6 Grade 2 anterolisthesis with flexion teardrop fracture of the anterior C6 with jumped facet on the right and perched facet on the left at C5–C6 with spinal canal stenosis. On September 12, 2019, an Individual Expanded Access Protocol was approved for administration of multiple infusions of autologous, adipose-derived MSCs (adMSCs) for the treatment of this quadriplegic incomplete C5-6 SCI patient. Thirty-four (34) recurrent infusions each with 200 million cells were administered, over a period of ∼2.5 years, which resulted in significant improvements in his quality-of-life as demonstrated by substantial improvements in SCIM-III (Spinal Cord Independence Measure III) scores. Additionally, electromyography/nerve conduction velocity (EMG/NCV) studies showed improvements in the patient's motor and sensory function. No safety concerns were presented, and no serious adverse events were reported during the entire course of treatment. Multiple intravenous infusions of autologous HB-adMSCs for treatment of SCI demonstrated significant enhancements in the patient's neurological function with improved quality-of-life. Further research is needed to evaluate the results of this study.

Effect of mesenchymal stromal cells transplantation on the outcomes of patients with knee osteoarthritis: A systematic review and meta-analysis.

Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.

Injection of Freshly Collected Adipose Tissue for the Treatment Complex Cryptoglandular Anal Fistula: Case Report

AbstractIntroduction Perianal fistula is a common colorectal disease which is caused mainly by cryptoglandular disease. Although most cases are treated successfully by surgery, management of complex perianal fistulas (CPAF) remains a challenge with limited results in recurrence and sometimes associated with fecal incontinence. The CPAF treatment with autologous adipose-derived mesenchymal stem cells (ASCs) had become a research hotspot. The technique started to be used in the treatment of Crohn's disease (CD) fistulas, where the studies showed safe and goods result from the procedure. Cultured ASCs have been used but this approach requires the preceding collection of adipose tissue, time for isolation of ASCs and subsequent in vitro expansion, need for laboratory facilities, and expertise in cell culturing. These factors have been getting over by using the commercially available alternative, allogenic ASCs. Treatment with allogeneic ASCs has shown good results in patients with CD fistulas, however with the disadvantage of being expensive. Objective To show that the injection with freshly collected adipose tissue is an alternative to treatment with autologous or allogenic ASCs with several advantages. Methods: In this case report, we show our first experience in the treatment of CPAF with the application of collected adipose tissue in a tertiary referral hospital from Belo Horizonte, Brazil. Results The patient had a good postoperative recuperation with a complete fistula healing after 8 months without adverse effects. Conclusion Injection with freshly collected adipose tissue is a promising and apparently safe sphincter-sparing technique in the treatment of CPAF.

Low-glucose culture environment can enhance the wound healing capability of diabetic adipose-derived stem cells

BackgroundApplication of autologous adipose-derived stem cells (ASC) for diabetic chronic wounds has become an emerging treatment option. However, ASCs from diabetic individuals showed impaired cell function and suboptimal wound healing effects. We proposed that adopting a low-glucose level in the culture medium for diabetic ASCs may restore their pro-healing capabilities.MethodsASCs from diabetic humans and mice were retrieved and cultured in high-glucose (HG, 4.5 g/L) or low-glucose (LG, 1.0 g/L) conditions. Cell characteristics and functions were investigated in vitro. Moreover, we applied diabetic murine ASCs cultured in HG or LG condition to a wound healing model in diabetic mice to compare their healing capabilities in vivo.ResultsHuman ASCs exhibited decreased cell proliferation and migration with enhanced senescence when cultured in HG condition in vitro. Similar findings were noted in ASCs derived from diabetic mice. The inferior cellular functions could be partially recovered when they were cultured in LG condition. In the animal study, wounds healed faster when treated with HG- or LG-cultured diabetic ASCs relative to the control group. Moreover, higher collagen density, more angiogenesis and cellular retention of applied ASCs were found in wound tissues treated with diabetic ASCs cultured in LG condition.ConclusionsIn line with the literature, our study showed that a diabetic milieu exerts an adverse effect on ASCs. Adopting LG culture condition is a simple and effective approach to enhance the wound healing capabilities of diabetic ASCs, which is valuable for the clinical application of autologous ASCs from diabetic patients.

Efficacy of autologous adipose-derived stem cells and fractional carbon dioxide laser in the treatment of atrophic linear scars

Background Atrophic linear scars are scars that exhibit indentation or depression in the skin below the level of the surrounding tissues. Hyperpigmentation or hypopigmentation may be present. They are often caused by surgery, burns, and trauma. Objective To evaluate the efficacy of autologous adipose-derived stem cells (ADSCs) combined with fractional carbon dioxide (CO2) laser in the treatment of atrophic linear scars. Patients and methods This randomized, controlled preliminary study included 20 patients aged 20–45 years of both sexes with facial atrophic linear scars. The patients were randomized systematically into two groups: group A (combined ADSCs and fractional CO2 laser procedure) and group B (fractional CO2 laser only) of 10 patients each. The scar was evaluated using the Vancouver scar scale, along with a subjective satisfaction questionnaire, and ultrasound skin analysis at baseline and 1 month after the third treatment session. Results All participants completed the study. The mean Vancouver scar scale score improved significantly from 3.60±0.69 to 1.20±0.79 and from 2.20±1.03 to 1.60±0.52 with fractional CO2 laser plus ADSCs and CO2 laser procedure, respectively (P<0.001). However, CO2 laser plus ADSCs was significantly superior. Ultrasound skin examination showed a statistically significant increase in dermal collagen density (thickness) in both groups. Conclusion Our study shows that treatment with CO2 laser exposure plus ADSCs is safe and more effective for atrophic linear scar management than CO2 laser exposure alone.

Clinical Efficacy and Safety of the Intra-articular Injection of Autologous Adipose-Derived Mesenchymal Stem Cells for Knee Osteoarthritis: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial

Background: Intra-articular injection of autologous culture-expanded adipose-derived mesenchymal stem cells (ADMSCs) has introduced a promising treatment option for knee osteoarthritis. Although the clinical efficacy and safety of ADMSCs have been reported, the treatment remains controversial owing to the small sample sizes and heterogeneous osteoarthritis grades in previous studies. Purpose: To assess the efficacy and safety of intra-articular injection of ADMSCs as compared with placebo in alleviating pain and improving functional capacity in a large sample of patients with knee osteoarthritis of Kellgren-Lawrence (K-L) grade 3. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This phase III multicenter clinical trial was a double-blind randomized controlled study that included 261 patients with K-L grade 3 symptomatic knee osteoarthritis who were administered a single injection of autologous culture-expanded ADMSCs or placebo. Clinical data were assessed at baseline and at 3 and 6 months after the injection. The primary endpoints were improvements in 100-mm visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for function at 6 months after the injection. The secondary endpoints included clinical and radiologic examinations and safety after injection. The changes in cartilage defects after injection were assessed by magnetic resonance imaging at 6 months. Results: The ADMSC and control groups included 125 and 127 patients available for follow-up, respectively. At 6 months, the ADMSC group showed significantly better improvements in 100-mm VAS (ADMSC vs control, 25.2 vs 15.5; P = .004) and total WOMAC score (21.7 vs 14.3; P = .002) as compared with the control group. The linear mixed model analysis indicated significantly better improvements in all clinical outcomes in the ADMSC group after 6 months. At 6 months, the ADMSC group achieved significantly higher proportions of patients above the minimal clinically important difference in 100-mm VAS and WOMAC score. Radiologic outcomes and adverse events did not demonstrate significant differences between the groups. No serious treatment-related adverse events were observed. Magnetic resonance imaging revealed no significant difference in change of cartilage defects between the groups at 6 months. Conclusion: Intra-articular injection of autologous culture-expanded ADMSCs provided significant pain relief and functional improvements in patients with K-L grade 3 osteoarthritis. Long-term results are needed to determine the disease-modifying effects of ADMSCs, such as structural changes, and the duration of effect of intra-articular injection of ADMSCs in knee osteoarthritis. Registration: NCT03990805 (ClinicalTrials.gov identifier).

Comparable Effects on Healing between Autologous Diabetic Adipose-Derived Stem Cells and Allogeneic Normal Counterparts.

Adipose-derived stem cell (ASC) therapy is considered a promising strategy for improving impaired wound healing, especially in diabetics. Although the therapeutic potential of allogeneic ASCs from healthy donors is naturally limited, that of autologous ASCs from diabetic patients is questionable. The aim of this study was to investigate the impact of diabetic ASCs in the treatment of diabetic wounds. Diabetic ASCs (DMA) and nondiabetic ASCs were isolated from db/db and C57BL/6J mice, and characterized by immunocytochemistry, proliferation, differentiation, and gene expression assays. The effects of both ASCs on healing were investigated using 36 male 10- to 12-week-old db/db mice. Wound size was measured semiweekly until day 28, and histologic and molecular analyses were performed at day 14. Both ASCs had fibroblast-like morphology and were CD44 + /CD90 + /CD34 - /CD45 - at passage 4. Compared with nondiabetic ASCs in vitro, DMA proliferative capability was restored by passage 4 ( P > 0.05). Although DMA osteogenesis was attenuated ( P < 0.01), both ASCs had similar adipogenesis and expressions of PPARγ/LPL/OCN/RUNX2 ( P > 0.05). In vivo experiments showed that, compared with phosphate-buffered saline control, both ASCs are comparable in improving wound healing ( P < 0.0001), angiogenesis ( P < 0.05), epithelial cell proliferation ( P < 0.05), and granulation tissue formation ( P < 0.0001). In both in vitro and in vivo murine models, DMAs have shown a comparable therapeutic capacity to normal ASCs in promoting diabetic wound healing by improving angiogenesis, reepithelialization, and granulation tissue formation. These results support clinical applications of autologous ASCs in diabetic wound treatments. This work has particular surgical relevance as it highlights a theoretical and clinical pathway to use diabetic patients' own ASCs to treat their wounds, bypassing any concerns of cross-host sourcing issues in regenerative medicine.

Recent advances in cell-based regenerative therapies for corneal disease.

With limited access of more than half the world's population to corneal transplantation, regenerative medicine may represent a promising alternative. This review explores the main advancements achieved in cell-based therapies for corneal epithelium, stroma, and endothelium during 2021-2022. Multiple surgical techniques have been developed for epithelial limbal stem cell replacement. Recent studies aimed to gain greater understanding and characterization of these techniques. Though no clear superiority could be demonstrated, simple limbal epithelial transplantation seems to have the most clinical and cost effectiveness. For stromal disease, autologous adipose-derived stem cells have shown favorable results. For endothelial dysfunction, the validity of intracameral cultivated allogeneic endothelial cell injection and Descemetorrhexis without endothelial keratoplasty, as well as the benefits of adjunctive rho-associated kinase inhibitors, were emphasized. A plethora of innovative cell-based regenerative therapies for corneal diseases have been developed in past years. While recent literature solidifies our knowledge, most studies are still in preliminary or preclinical stages. Though showing great promise, these approaches will require larger studies with better-defined endpoints to establish their benefits over currently available treatments.

Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears

Influence of autologous adipose stem cell matrix gel on wound healing and scar hyperplasia of full-thickness skin defects in rabbit ears

Use of autologous adipose stem cell for the treatment of recurring and complex anal fistula

Use of autologous adipose stem cell for the treatment of recurring and complex anal fistula

Comparative study between enriching fat grafting with autologous adipose-derived stem cells and traditional fat transfer for facial tissue augmentation

Comparative study between enriching fat grafting with autologous adipose-derived stem cells and traditional fat transfer for facial tissue augmentation

Use of autologous adipose-derived mesenchymal stem cells for ovarian rejuvenation in poor responder IVF patients: a phase 1 randomized placebo-controlled double-blind crossover study

Background: Despite the application of various methods to augment ovarian responsiveness, the management of poor ovarian responders remains challenging and pregnancy rates following in vitro fertilization are poor. Advances in adult stem cell research and their clinical application has prompted interest in their use in assisted reproduction. We report the first double-blind, randomized, placebo-controlled clinical study using autologous human stromal vascular fraction (SVF) containing adipose-derived stem cells (ADSCs) for ovarian rejuvenation. Materials and methods: Thirty patients were recruited. Twenty-one had lower-than-expected reserves for their age and 9 had premature ovarian insufficiency. Patients were randomized into a placebo group (10) and an intervention group (20). SVF was obtained from adipose tissue following abdominal liposuction; the ADSC component was characterized using flow cytometry. Three equal insertions, adjusted based on ovarian volume, were performed at monthly intervals via an ultrasound-guided transvaginal needle puncture. The SVF was not cultured before transplantation. Those in the placebo group were then crossed over to the intervention group and received a single SVF (maximally concentrated) insertion (crossover group). Results: The median viable SVF cell number inserted per patient over 3 months, and the percentage of mesenchymal stem cells (MSC) thereof, was 1.6×106 and 13.2%, respectively. Resulting anti-Mullerian hormone (AMH) changes were variable over the treatment course with a notable placebo effect. Patients with premature ovarian insufficiency showed no change in AMH, both to intervention and placebo. Despite this, a temporary return of menses was noted in a third of patients while on treatment. Patients with low reserves for age showed an increase in AMH, although not statistically significant when compared to placebo. In the crossover group, insertions were limited to one intervention comprising all cells; here a significantly higher median of 3.4×106 SVF cells were injected containing an average of 16.9% MSCs. No significant change in AMH was noted. To date 12 patients have undergone ovarian stimulation and in vitro fertilization after stem cell therapy; of these 9 have had embryo transfers with a resulting pregnancy rate of 33%. There were also 2 spontaneous pregnancies. Conclusion: Although the application of SVF-derived ADSCs for ovarian rejuvenation remains experimental, the current study provides further support for the safety of this approach and presents encouraging results as to its efficacy in assisted reproduction.

Functional enhancement of acute infracted heart by coinjection of autologous adipose-derived stem cells with matrigel.

Recent clinical developments in tissue bioengineering have applications in acute cardiac ischemia and infarction and include the use of stem cells that combine injectable scaffold material. This study aimed to evaluate the effects of adipose-derived stem cells (ADSCs) that combine the Matrigel scaffold on cardiac morphology/functions. The autologous ADSCs myocardial infarction (MI) model was induced by the permanent ligation method of the left anterior descending coronary artery (LAD). MI-operated rats were randomly divided into PBS group, Matrigel group, PBS plus ADSCs group (PBS+ADSCs), and Matrigel plus ADSCs group (Matrigel+ADSCs). Matrigel was used as an injectable scaffold. Rats with a 1-week-old myocardial infarction were injected with 2 × 106 labeled ADSCs in the border area of the ischemic heart. Heart function was determined by echocardiography. The hemodynamics, cardiac structure, and graft characteristics were evaluated. The ADSCs were successfully isolated and identified, demonstrating a good proliferative status and cell retention in the Matrigel. ADSCs+Matrigel exhibited the most improved heart functions (LVESD, LVEDD, LVFS, LVEF) compared to those of other groups (p < 0.05). ADSCs+Matrigel significantly reduced infarct size compared to other groups (p < 0.05). Cotransplantation of ADSCs and Matrigel showed the best effect on maintaining the thickness of the ventricular wall compared to the other groups (p < 0.05). Engrafted ADSCs played a role in the formation of the neovasculature in myocardial infarction. ADSCs+Matrigel triggered the greatest enhancement in arteriole density than other groups (p < 0.05). Cotransplanting with ADSCs and Matrigel showed significantly higher levels of cardiac troponin T (cTnT), NK2-transcription factor related locus-5 (Nkx2.5), von Willebrand factor (vWF) than the other groups (p < 0.05). In conclusion, this study demonstrated that cotransplanting ADSCs with Matrigel resulted in improved cardiac morphology and cardiac function in the rat model of myocardial infarction.