•Cell-free therapy using MSC-CM can offer an exciting approach in regenerative medicine.•Therapeutic role of cytokine and growth factors present in MSC-CM in clinical studies.•Cell-free therapy ...offers a significant advantage over cells based therapy and other conventional pharmaceutics.
Mesenchymal Stem Cells (MSCs) have been shown to be a promising candidate for cell-based therapy. The therapeutic potential of MSCs, towards tissue repair and wound healing is essentially based on their paracrine effects. Numerous pre-clinical and clinical studies of MSCs have yielded encouraging results. Further, these cells have been shown to be relatively safe for clinical applications. MSCs harvested from numerous anatomical locations including the bone marrow, adipose tissue, Wharton’s jelly of the umbilical cord etc., display similar immunophenotypic profiles. However, there is a large body of evidence showing that MSCs secrete a variety of biologically active molecules such as growth factors, chemokines, and cytokines. Despite the similarity in their immunophenotype, the secretome of MSCs appears to vary significantly, depending on the age of the host and niches where the cells reside. Thus, by implication, proteomics-based profiling suggests that the therapeutic potential of the different MSC populations must also be different. Analysis of the secretome points to its influence on varied biological processes such as angiogenesis, neurogenesis, tissue repair, immunomodulation, wound healing, anti-fibrotic and anti-tumour for tissue maintenance and regeneration. Though MSC based therapy has been shown to be relatively safe, from a clinical standpoint, the use of cell-free infusions can altogether circumvent the administration of viable cells for therapy. Understanding the secretome of in vitro cultured MSC populations, by the analysis of the corresponding conditioned medium, will enable us to evaluate its utility as a new therapeutic option. This review will focus on the accumulating evidence that points to the therapeutic potential of the conditioned medium, both from pre-clinical and clinical studies. Finally, this review will emphasize the importance of profiling the conditioned medium for assessing its potential for cell-free therapy therapy.
Mesenchymal stem cells (MSCs) have immense potential for cell-based therapy of acute and chronic pathological conditions. MSC transplantation for cell-based therapy requires a substantial number of ...cells in the range of 0.5-2.5 × 10
cells/kg body weight of an individual. A prolific source of MSCs followed by in vitro propagation is therefore an absolute prerequisite for clinical applications. Umbilical cord tissue (UCT) is an abundantly available prolific source of MSC that are fetal in nature and have higher potential for ex-vivo expansion. However, the ex-vivo expansion of MSCs using a xenogeneic supplement such as fetal bovine serum (FBS) carries the risk of transmission of zoonotic infections and immunological reactions. We used platelet lysate (PL) as a xeno-free, allogeneic replacement for FBS and compared the biological and functional characteristics of MSC processed and expanded with PL and FBS by explant and enzymatic method. UCT-MSCs expanded using PL displayed typical immunophenotype, plasticity, immunomodulatory property and chromosomal stability. PL supplementation also showed 2-fold increase in MSC yield from explant culture with improved immunomodulatory activity as compared to enzymatically dissociated cultures. In conclusion, PL from expired platelets is a viable alternative to FBS for generating clinically relevant numbers of MSC from explant cultures over enzymatic method.
The present work is focused on the leaching and separation of Co and Mn from electrode material of spent lithium-ion batteries. The influences of different process parameters like HCl concentration, ...time, and temperature on the leaching of Co and Mn are studied. Higher than 99% leaching efficiencies of Co and Mn were obtained in 90 min using 1.75 M HCl at 50 °C. In the subsequent precipitation study, Mn was removed selectively from the leach solution by using sodium hypochlorite solution (1.5 times stoichiometric requirement) at a pH of 1.5 in 30 min. X-ray diffraction analysis of precipitated manganese indicate the presence of mixtures of manganese oxides (MnO2, Mn3O4 and Na0.55Mn2O4.1.5H2O). Cobalt in the Mn free solution was precipitated by using sodium carbonate solution after removing the traces amount of Al and Cu. Overall recovery of Mn and Co is 95% and 90%, respectively in pilot scale. The flow sheet proposed for the leaching and separation of Co and Mn is of a simple and efficient technique for the recycling industries.
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•Hydrochloric acid is used for leaching of the electrode materials of spent LIBs.•Higher than 99% leaching efficiency is observed for both Co and Mn.•Mn was selectively separated from Co at low pH using sodium hypochlorite.•Overall recovery for Co and Mn are 90% and 95%, respectively.•Flow sheet proposed for commercial application.
Androgens responsible for male sexual differentiation in utero are produced by Leydig cells in the fetal testicular interstitium. Leydig cells rarely proliferate and, hence, rely on constant ...differentiation of interstitial progenitors to increase their number during fetal development. The cellular origins of fetal Leydig progenitors and how they are maintained remain largely unknown. Here we show that Notch-active, Nestin-positive perivascular cells in the fetal testis are a multipotent progenitor population, giving rise to Leydig cells, pericytes, and smooth muscle cells. When vasculature is disrupted, perivascular progenitor cells fail to be maintained and excessive Leydig cell differentiation occurs, demonstrating that blood vessels are a critical component of the niche that maintains interstitial progenitor cells. Additionally, our data strongly supports a model in which fetal Leydig cell differentiation occurs by at least two different means, with each having unique progenitor origins and distinct requirements for Notch signaling to maintain the progenitor population.
Human skin is body's vital organ constantly exposed to abiotic oxidative stress. This can have deleterious effects on skin such as darkening, skin damage, and aging. Plant-derived products having ...skin-protective effects are well-known traditionally. Triphala, a formulation of three fruit products, is one of the most important rasayana drugs used in Ayurveda. Several skin care products based on Triphala are available that claim its protective effects on facial skin. However, the skin protective effects of Triphala extract (TE) and its mechanistic action on skin cells have not been elucidated in vitro. Gallic acid, ellagic acid, and chebulinic acid were deduced by LC-MS as the major constituents of TE. The identified key compounds were docked with skin-related proteins to predict their binding affinity. The IC50 values for TE on human dermal fibroblasts (HDF) and human keratinocytes (HaCaT) were 204.90 ± 7.6 and 239.13 ± 4.3 μg/mL respectively. The antioxidant capacity of TE was 481.33 ± 1.5 mM Trolox equivalents in HaCaT cells. Triphala extract inhibited hydrogen peroxide (H2O2) induced RBC haemolysis (IC50 64.95 μg/mL), nitric oxide production by 48.62 ± 2.2%, and showed high reducing power activity. TE also rescued HDF from H2O2-induced damage; inhibited H2O2 induced cellular senescence and protected HDF from DNA damage. TE increased collagen-I, involucrin and filaggrin synthesis by 70.72 ± 2.3%, 67.61 ± 2.1% and 51.91 ± 3.5% in HDF or HaCaT cells respectively. TE also exhibited anti-tyrosinase and melanin inhibition properties in a dose-dependent manner. TE increased the mRNA expression of collagen-I, elastin, superoxide dismutase (SOD-2), aquaporin-3 (AQP-3), filaggrin, involucrin, transglutaminase in HDF or HaCaT cells, and decreased the mRNA levels of tyrosinase in B16F10 cells. Thus, Triphala exhibits protective benefits on skin cells in vitro and can be used as a potential ingredient in skin care formulations.
From the beginning of humanity, our generation has been on the edge of finding suitable solutions to increase the product’s life-cycle and reduce the environmental impact of the product. Life-cycle ...assessment is a process to evaluate the effects of products or services whereas environmental impact assessment is an inter-related process of evaluating the environmental impact of a product or service. Plant fibre reinforced composites are developed by researchers, which are kindled by economic and environmental trepidations. The forest’s wood resources will decline and deplete due to environmental issues caused by natural and renewable resources. The main objective of this review is to conduct life-cycle assessment and environmental impact assessment studies on plant fibres and manufacturing of bio-composites from these fibres. It identifies the differences and causes to the environment, in particular about the total effect on the surrounding atmosphere. Another aim of this work is to assess a techno-economic feasibility based on the environmental impact category. In addition to this, inventory assessments of these composites are also dealt with, alongside the industrial applications. This review concludes a summary of current research and point out the opportunities and challenges for future researchers.
With the increasing aging population and progressive nature of the disease, Alzheimer’s disease (AD) poses to be an oncoming epidemic with limited therapeutic strategies. It is characterized by ...memory loss, behavioral instability, impaired cognitive function, predominantly, cognitive inability manifested due to the accumulation of β-amyloid, with malfunctioned cholinergic system. Rivastigmine, a reversible dual cholinesterase inhibitor, is a more tolerable and widely used choice of drug for AD. However, rivastigmine being hydrophilic and undergoing the first-pass metabolism exhibits low CNS bioavailability. Nanoformulations including liposomes and PLGA nanoparticles can encapsulate hydrophilic drugs and deliver them efficiently to the brain. Besides, the nasal route is receiving considerable attention recently, due to its direct access to the brain. Therefore, the present study attempts to evaluate the pharmacokinetic and pharmacodynamic properties of nasal liposomal and PLGA nanoparticle formulations of rivastigmine in acute scopolamine-induced amnesia and chronic colchicine induced cognitive dysfunction animal models, and validate the best formulation by employing pharmacokinetic and pharmacodynamic (PK-PD) modeling. Nasal liposomal rivastigmine formulation showed the best pharmacokinetic features with rapid onset of action (Tmax = 5 min), higher Cmax (1489.5 ± 620.71), enhanced systemic bioavailability (
F
= 118.65 ± 23.54; AUC = 35,921.75 ± 9559.46), increased half-life (30.92 ± 8.38 min), and reduced clearance rate (Kel (1/min) = 0.0224 ± 0.006) compared to oral rivastigmine (Tmax = 15 min; Cmax = 56.29 ± 27.05;
F
= 4.39 ± 1.82; AUC = 1663.79 ± 813.54; t1/2 = 13.48 ± 5.79; Kel (1/min) = 0.0514 ± 0.023). Further, the liposomal formulation significantly rescued the memory deficit induced by scopolamine as well as colchicine superior to other formulations as assessed in Morris water maze and passive avoidance tasks. PK-PD modeling demonstrated a strong correlation between the pharmacokinetic parameters and acetylcholinesterase inhibition of liposomal formulation.
Regardless of progress in therapy management which are developed for colon cancer (CC), it remains the third most common cause of mortality due to cancers around the world. Conventional medicines ...pose side effects due to untoward action on non-target cells. Their inability to deliver drugs to the affected regions of the colon locally, in a reproducible manner raises a concern towards the efficacy of therapy. In this regard, nanoparticles emerged as a promising drug delivery system due to their flexibility in designing, drug release modulation and cancer cell targeting. Not only are nanoparticles making their way into colon cancer research in the revolution of conventional onco-therapeutics, but they also offer promising scope in the development of colon cancer vaccines and theranostic tools. However, there are challenges with respect to drug delivery using nanoparticles, which may hamper the delivery of these novel carriers to the colon. The present review addresses recent advents in nanotechnology for colon-specific drug delivery (CDDS) which may help to overcome the existing challenges and intends to recognize futuristic potentials in the treatment of CC with CDDS.
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•Existing status of colon cancer and strategies to manage them using nanotechnology.•Nanoformulations for delivery of anticancer drugs to colon.•Effective strategies for delivering nanocarriers to the target site.•Challenges for treating nanocarriers to colon cancer.
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