Earlier research primarily attributed the effects of mesenchymal stem cell (MSC) therapies to their capacity for local engrafting and differentiating into multiple tissue types. However, recent studies have revealed that implanted cells do not survive for long, and that the benefits of MSC therapy could be due to the vast array of bioactive factors they produce, which play an important role in the regulation of key biologic processes. Secretome derivatives, such as conditioned media or exosomes, may present considerable advantages over cells for manufacturing, storage, handling, product shelf life and their potential as a ready-to-go biologic product. Nevertheless, regulatory requirements for manufacturing and quality control will be necessary to establish the safety and efficacy profile of these products. Among MSCs, human uterine cervical stem cells (hUCESCs) may be a good candidate for obtaining secretome-derived products. hUCESCs are obtained by Pap cervical smear, which is a less invasive and painful method than those used for obtaining other MSCs (for example, from bone marrow or adipose tissue). Moreover, due to easy isolation and a high proliferative rate, it is possible to obtain large amounts of hUCESCs or secretome-derived products for research and clinical use.

https://www.mdpi.com/1422-0067/18/9/1852/pdf

Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine

Advancing biomaterials of human origin for tissue engineering

Nowadays, magnetic hyperthermia constitutes a complementary approach to cancer treatment. The use of magnetic particles as heating mediators, proposed in the 1950s, provides a novel strategy for improving tumor treatment and, consequently, patient's quality of life. This review reports a broad overview about several aspects of magnetic hyperthermia addressing new perspectives and the progress on relevant features such as the ad hoc preparation of magnetic nanoparticles, physical modeling of magnetic heating, methods to determine the heat dissipation power of magnetic colloids including the development of experimental apparatus and the influence of biological matrices on the heating efficiency.

Fundamentals and advances in magnetic hyperthermia

The mesenchymal stem cell (MSC) is being broadly studied in clinical trials. Contrary to the early paradigm of cell replacement and differentiation as a therapeutic mechanism of action, evidence is mounting that the secretions of the cells are responsible for their therapeutic effects. These secretions include molecules and extracellular vesicles that have both local and distant effects. This review summarizes the up- and down-regulation of MSC anti-inflammatory, immune modulating, anti-tumor, and regenerative secretions resulting from different stimuli including: a) hypoxia, which increases the production of growth factors and anti-inflammatory molecules; b) pro-inflammatory stimuli that induce the secretion of immune modulating and anti-inflammatory factors; and c) 3 dimensional growth which up regulates the production of anti-cancer factors and anti-inflammatory molecules compared to monolayer culture. Finally we review in detail the most important factors present in conditioned medium of MSC that can be considered protagonists of MSC physiological effects including HGF, TGF-b, VEGF, TSG-6, PGE2 and galectins 1, and 9. We conclude that there is potential for the development of acellular therapeutic interventions for autoimmune, inflammatory, and malignant diseases and tissue regeneration from cellular secretions derived from MSCs cultured under the appropriate conditions.

/pdf/a-review-of-therapeutic-effects-of-mesenchymal-stem-cell-2ppkmxfnef.pdf

A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods

A review of chitosan and its derivatives in bone tissue engineering.

Cell-based regenerative therapies, based on in vitro propagation of stem cells, offer tremendous hope to many individuals suffering from degenerative diseases that were previously deemed untreatable. Due to the self-renewal capacity, multilineage potential, and immunosuppressive property, mesenchymal stem cells (MSCs) are considered as an attractive source of stem cells for regenerative therapies. However, poor growth kinetics, early senescence, and genetic instability during in vitro expansion and poor engraftment after transplantation are considered to be among the major disadvantages of MSC-based regenerative therapies. A number of complex inter- and intracellular interactive signaling systems control growth, multiplication, and differentiation of MSCs in their niche. Common laboratory conditions for stem cell culture involve ambient O2 concentration (20%) in contrast to their niche where they usually reside in 2–9% O2. Notably, O2 plays an important role in maintaining stem cell fate in terms of proliferation and differentiation, by regulating hypoxia-inducible factor-1 (HIF-1) mediated expression of different genes. This paper aims to describe and compare the role of normoxia (20% O2) and hypoxia (2–9% O2) on the biology of MSCs. Finally it is concluded that a hypoxic environment can greatly improve growth kinetics, genetic stability, and expression of chemokine receptors during in vitro expansion and eventually can increase efficiency of MSC-based regenerative therapies.

/pdf/hypoxic-culture-conditions-as-a-solution-for-mesenchymal-1ieadb6kd4.pdf

Hypoxic Culture Conditions as a Solution for Mesenchymal Stem Cell Based Regenerative Therapy

http://eprints.um.edu.my/2371/2/Inherent_Differential_Propensity_of_Dental_Pulp_Stem_Cells_Derived_from_Human_Deciduous_and_Permanent_Teeth.pdf

Inherent Differential Propensity of Dental Pulp Stem Cells Derived from Human Deciduous and Permanent Teeth

Effects of different implant-abutment connections on micromotion and stress distribution: prediction of microgap formation

Recent studies suggest that the main driving force behind the therapeutic activity observed in mesenchymal stem cells (MSCs) are the paracrine factors secreted by these cells. These biomolecules also trigger antiapoptotic events to prevent further degeneration of the diseased organ through paracrine signalling mechanisms. In comparison with the normal physiological conditions, an increased paracrine gradient is observed within the peripheral system of diseased organs that enhances the migration of tissue-specific MSCs towards the site of infection or injury to promote healing. Thus, upon administration of conditioned media derived from mesenchymal stem cell cultures (MSC-CM) could contribute in maintaining the increased paracrine factor gradient between the diseased organ and the stem cell niche in order to speed up the process of recovery. Based on the principle of the paracrine signalling mechanism, MSC-CM, also referred as the secretome of the MSCs, is a rich source of the paracrine factors and are being studied extensively for a wide range of regenerative therapies such as myocardial infarction, stroke, bone regeneration, hair growth, and wound healing. This article highlights the current technological applications and advances of MSC-CM with the aim to appraise its future potential as a regenerative therapeutic agent.

Noor Hayaty Abu Kasim

Papers

Hypoxic Culture Conditions as a Solution for Mesenchymal Stem Cell Based Regenerative Therapy

Inherent Differential Propensity of Dental Pulp Stem Cells Derived from Human Deciduous and Permanent Teeth

Effects of different implant-abutment connections on micromotion and stress distribution: prediction of microgap formation

Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine.

Tissue-Mimicking Gel Phantoms for Thermal Therapy Studies