Stromal vascular fraction (SVF), derived enzymatically or mechanically from adipose tissue, contains a heterogenous population of cells and stroma, including multipotent stem cells. The regenerative capacity of SVF may potentially be adapted for a broad range of clinical applications, including the healing of acute cutaneous wounds.

Thanks to their biological properties, amniotic membrane (AM), and its derivatives are considered as an attractive reservoir of stem cells and biological scaffolds for bone regenerative medicine. The objective of this systematic review was to assess the benefit of using AM and amniotic membrane-derived products for bone regeneration. An electronic search of the MEDLINE-Pubmed database and the Scopus database was carried out and the selection of articles was performed following PRISMA guidelines. This systematic review included 42 articles taking into consideration the studies in which AM, amniotic-derived epithelial cells (AECs), and amniotic mesenchymal stromal cells (AMSCs) show promising results for bone regeneration in animal models. Moreover, this review also presents some commercialized products derived from AM and discusses their application modalities. Finally, AM therapeutic benefit is highlighted in the reported clinical studies. This study is the first one to systematically review the therapeutic benefits of AM and amniotic membrane-derived products for bone defect healing. The AM is a promising alternative to the commercially available membranes used for guided bone regeneration. Additionally, AECs and AMSCs associated with an appropriate scaffold may also be ideal candidates for tissue engineering strategies applied to bone healing. Here, we summarized these findings and highlighted the relevance of these different products for bone regeneration.

Background: Some studies have reported results from the use of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) to treat osteoarthritis (OA). Objective: To evaluate the efficacy of MSC-EVs as a treatment for OA. Data sources: Databases were searched using the terms 'mesenchymal stem cells', 'osteoarthritis' and 'extracellular vesicles.' Study eligibility criteria: Studies performed in animal models utilizing MSC-EVs to treat OA that described the macroscopic evaluation or histological evaluation were included. Study appraisal: The quality of the studies was examined using the CAMARADES quality checklist. Results: MSC-EVs were superior to the placebo in the macroscopic evaluation and histological evaluation. MSC-EVs were more effective in the early stage of OA and once a week was better than multiple times a week. Limitations: The included studies were highly heterogeneous. Conclusion: MSC-EVs may improve the results of macroscopic and histological evaluations of OA.

Stem cell therapy is increasingly used for knee osteoarthritis (KOA). We aimed to review the evidence of autologous mesenchymal stem cell therapy on pain, function and severity on imaging in KOA.

The aim of this systematic review is to investigate different diagnostic methods and the available treatment options for subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

Nonscarring alopecia, including androgenetic alopecia and alopecia areata, are common and can negatively impact quality of life. Recent clinical studies have investigated autologous, adipose-derived stromal vascular fraction (SVF) as a potentially beneficial treatment option.

This review assesses regenerative medicine of the upper aerodigestive tract during the first two decades of the twenty-first century, focusing on end-stage fibrosis and tissue loss in the upper airways, salivary system, oropharynx and tongue.

COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.

SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins secreted by sustentacular cells in order to be processed by olfactory receptor neurons. Olfactory disorder is one of the main manifestations of COVID-19, however, research is still required to clarify the mechanism involved in SARS-CoV-2 induced anosmia.

To assess whether biologic augmentation in addition to core decompression (CD), compared with CD alone, improves clinical and radiographic outcomes in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH). Our hypothesis was that biologic augmentation would reduce the progression of osteonecrosis and therefore also the rate of conversion to total hip arthroplasty (THA).

This systematic review focus on the application of bilayer scaffolds as an engaging structure for the engineering of multilayered tissues, including vascular and osteochondral tissues, skin, nerve, and urinary bladder. This article provides a concise literature review of different types of bilayer scaffolds to understand their efficacy in targeted tissue engineering.

Animal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells (ADSCs). Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson's disease (PD). Here, eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention. Quality assessment was conducted using a 10-item risk of bias tool. For the subsequent meta-analysis, study characteristics were extracted and effect sizes were computed. Ten out of 2324 published articles (n = 169 animals) were selected for further meta-analysis. After ADSC therapy, the rotation behavior (10 experiments, n = 156 animals) and rotarod performance (3 experiments, n = 54 animals) were improved (P < 0.000 01 and P = 0.000 3, respectively). The rotation behavior test reflected functional recovery, which may be due to the neurogenesis from neuronally differentiated ADSCs, resulting in a higher pooled effect size of standard mean difference (SMD) (- 2.59; 95% CI, - 3.57 to - 1.61) when compared to that of primitive cells (- 2.18; 95% CI, - 3.29 to - 1.07). Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term effect. Following the transplantation of ADSCs, tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36 [6.85, 19.86]. Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of PD. The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects. The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.

Exercise training promotes muscle adaptation and remodelling by balancing the processes of anabolism and catabolism; however, the mechanisms by which exercise delays accelerated muscle wasting are not fully understood. Intramuscular extracellular matrix (ECM) proteins are essential to tissue structure and function, as they create a responsive environment for the survival and repair of the muscle fibres. However, their role in muscle adaptation is underappreciated and underinvestigated. The PubMed, COCHRANE, Scopus and CIHNAL databases were systematically searched from inception until February 2021. The inclusion criteria were on ECM adaptation after exercise training in healthy adult population. Evidence from 21 studies on 402 participants demonstrates that exercise training induces muscle remodelling, and this is accompanied by ECM adaptation. All types of exercise interventions promoted a widespread increase in collagens, glycoproteins and proteoglycans ECM transcriptomes in younger and older participants. The ECM controlling mechanisms highlighted here were concerned with myogenic and angiogenic processes during muscle adaptation and remodelling. Further research identifying the mechanisms underlying the link between ECMs and muscle adaptation will support the discovery of novel therapeutic targets and the development of personalised exercise training medicine.

Glioblastoma (GBM), the most frequent and aggressive glial tumor, is currently treated as first line by the Stupp protocol, which combines, after surgery, radiotherapy and chemotherapy. For recurrent GBM, in absence of standard treatment or available clinical trials, various protocols including cytotoxic drugs and/or bevacizumab are currently applied. Despite these heavy treatments, the mean overall survival of patients is under 18 months. Many clinical studies are underway. Based on clinicaltrials.org and conducted up to 1 April 2020, this review lists, not only main, but all targeted therapies in phases II-IV of 257 clinical trials on adults with newly diagnosed or recurrent GBMs for the last twenty years. It does not involve targeted immunotherapies and therapies targeting tumor cell metabolism, that are well documented in other reviews. Without surprise, the most frequently reported drugs are those targeting (i) EGFR (40 clinical trials), and more generally tyrosine kinase receptors (85 clinical trials) and (ii) VEGF/VEGFR (75 clinical trials of which 53 involving bevacizumab). But many other targets and drugs are of interest. They are all listed and thoroughly described, on an one-on-one basis, in four sections related to targeting (i) GBM stem cells and stem cell pathways, (ii) the growth autonomy and migration, (iii) the cell cycle and the escape to cell death, (iv) and angiogenesis.

Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against S. aureus. Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.

Spinal cord injury (SCI) is a severe traumatic disease of the central nervous system, with a global prevalence of 236-4187 per million people. This meta-analysis aimed to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) in treating patients with SCI as well as the optimal source and transplantation method of MSCs. PubMed, OVID, Cochrane, Web of Science, and China Biomedical Database were searched up until April 01, 2021. The study was conducted for five endpoints: American Spinal Injury Association (ASIA) motor and sensory score, ASIA grade improvement, Barthel Index (BI), and adverse reactions. Standard meta-analysis and network meta-analysis were performed using Stata 14.0. Eighteen studies with a total of 949 patients, were included in the meta-analysis. Standard meta-analysis showed that MSCs significantly improved ASIA motor score (P < 0.001), sensory score (P < 0.001), ASIA grade (P < 0.001), and BI (P < 0.001) compared to rehabilitation. In addition, in the network meta-analysis, autologous MSCs significantly improved the ASIA motor [MD = 8.01, 95% CI (4.27, 11.76)], sensory score [MD = 17.98, 95% CI (10.04, 25.91)], and BI [MD = 7.69, 95% CI (2.10, 13.29)] compared to rehabilitation. Similarly, compared to rehabilitation, intrathecal injection (IT) of MSCs significantly improved the ASIA motor [MD = 7.97, 95% CI (4.40, 11.53)] and sensory score [MD = 19.60, 95% CI (9.74, 29.46)]. Compared to rehabilitation, however, only the IL of MSCs was associated with more adverse reactions [OR = 17.82, 95% CI (2.48, 128.22)]. According to the results of SUCRA, both autologous MSCs and IT transplantation approaches most improved the neurological function in SCI patients. Cell transplantation using MSCs is effective in patients with SCI and IT of autologous MSCs may be more beneficial.

Extracellular vesicles from mesenchymal stromal cells (MSC-EVs) have shown promise in wound healing. Their use in diabetic wounds specifically, however, remains pre-clinical and their efficacy remains uncertain less clear. A systematic review of preclinical studies is needed to determine the efficacy of MSC-EVs in the treatment of diabetic wounds to accelerate the clinical translation of this cell-based therapy.

Mesenchymal stem cells (MSC) are adult multi-potent cells that can be isolated from many types of tissues including adipose tissue, bone marrow, and umbilical cord. They show great potential for cell therapy-based treatments, which is why they are being used in numerous clinical trials for a wide range of diseases. However, the success of placebo-controlled clinical trials has been limited, so new ways of improving the therapeutic effects of MSC are being developed, such as their assembly in a 3D conformation. In this meta-analysis, we review aggregate formation, in vitro functional properties and in vivo therapeutic potential displayed by adipose tissue, bone marrow, and umbilical cord-derived MSC, assembled as spheroids. The databases PubMed and SciELO were used to find eligible articles, using free-words and MeSH terms related to the subject, finding 28 published articles meeting all inclusion and exclusion criteria. Of the articles selected 15 corresponded to studies using MSC derived from bone marrow, 10 from adipose tissue and 3 from umbilical cord blood or tissue. The MSC spheroids properties analyzed that displayed enhancement in comparison with monolayer 2D culture, are stemness, angiogenesis, differentiation potential, cytokine secretion, paracrine and immunomodulatory effects. Overall studies reveal that the application of MSC spheroids in vivo enhanced therapeutic effects. For instance, research exhibited reduced inflammation, faster wound healing, and closure, functional recovery and tissue repair due to immunomodulatory effects, better MSC engraftment in damaged tissue, higher MSC survival and less apoptosis at the injury. Still, further research and clinical studies with controlled and consistent results are needed to see the real therapeutic efficacy of MSC spheroids.

The recent advances in the field of cell-based therapeutics open promising perspectives for oral tissue regeneration. The development of large animal models, which overcome the limits of the rodent models and allow to emulate clinical situations, is crucial for the validation of regenerative strategies to move toward clinical application. Currently, porcine, canine, and ovine models are mainly developed for oral regeneration and their specific characteristics have an impact on the outcomes of the studies. Thus, this systematic review investigates the application of porcine, canine, and ovine models in present cell-based oral regeneration, according to the species characteristics and the targeted tissue to regenerate. A customized search of PubMed, EMBASE, Scopus, and Web of Science databases from January 2015 to March 2020 was conducted. Relevant articles about cell-based oral tissues engineering in porcine, canine, and ovine models were evaluated. Among the evaluated articles, 58 relevant studies about cell-based oral regeneration in porcine, canine, and ovine models matched the eligibility criteria and were selected for full analysis. Porcine models, the most similar species with humans, were mostly used for bone and periodontium regeneration; tooth regeneration was reported only in pig, except for one study in dog. Canine models were the most transversal models, successfully involved for all oral tissue regeneration and notably in implantology. However, differences with humans and ethical concerns affect the use of these models. Ovine models, alternative to porcine and canine ones, were mainly used for bone and, scarcely, periodontium regeneration. The anatomy and physiology of these animals restrain their involvement. If consistency was found in defect specificities and cell trends among different species animal models of bone, dentin-pulp complex, or tooth regeneration, variability appeared in periodontium. Regeneration assessment methods were more elaborate in porcines and canines than in ovines. Risk of bias was low for selection, attrition and reporting, but unclear for performance and detection. Overall, if none of the large animal models can be considered an ideal one, they are of deemed importance for oral cell-based tissue engineering and researchers should consider their relevance to establish favorable conditions for a given preclinical cell-based therapeutics. Impact statement This systematic review investigates porcine, canine, and ovine models for current oral cell-based regeneration procedures, and researchers could refer to it for the choice of the most pertinent preclinical model for a given cell-based therapeutics.

Thalassaemia is an autosomal recessive blood disorder, caused by mutations in globin genes or their regulatory regions, resulting in a reduced rate of synthesis of one of the globin chains that make up haemoglobin. In β-thalassaemia there is an underproduction of β-globin chains combined with excess of free α-globin chains. The excess free α-globin chains precipitate in red blood cells, leading to their increased destruction (haemolysis) and ineffective erythropoiesis. The conventional treatment is based on the correction of haemoglobin through regular red blood cell transfusions and treating the iron overload that develops subsequently with iron chelation therapy. Although, early detection and initiations of such supportive treatment has improved the quality of life for people with transfusion-dependent thalassaemia, allogeneic hematopoietic stem cell transplantation is the only widely available therapy with a curative potential. Gene therapy for β-thalassaemia has recently received conditional authorisation for marketing in Europe, and may soon become widely available as another alternative therapy with curative potential for people with transfusion-dependent thalassaemia. This is an update of a previously published Cochrane Review.