Current Stem Cell Research & Therapy - Volume 8, Issue 2, 2013

Human amniotic fluid cells have been used traditionally as a diagnostic tool for genetic anomalies. More recently it has been recognized that amniotic fluid contains populations of stem cells. Mesenchymal stem cells (AFMSC) were first to be described. These cells are able to differentiate towards mesodermal lineages. More recently cells with broader potential, defined as amniotic fluid stem cells (AFSC), were also isolated. They have intermediate characteristics between embryonic and adult stem cells and are able to differentiate into lineages representative of all three germ layers but unlike ES cells they do not form tumours in vivo. Furthermore, AFSC have been reverted to functional pluripotency in a transgene-free approach using an epigenetics modifier. These characteristics, together with absence of ethical issues concerning their employment, have made stem cells from amniotic fluid a promising candidate for cell therapy and tissue engineering.

Recent studies support cell based therapies for several diseases. Human fetal stem cells have received much attention for developing new therapeutic strategies. Recently, our group and others have successfully isolated and expanded karyotypically normal stem cells from an alternative fetal source, the human second trimester amniotic fluid (AF) and performed a systematic phenotypic and molecular analysis. The main characteristics of amniotic fluid stem cells (hAFSCs) are their fetal origin, the high number of isolated cells, their wide differentiation properties and their rapid expansion in vitro. These characteristics render hAFSCs as a very attractive tool for clinical applications based on cell therapy. The use of hAFSC transplantation has been studied in a variety of disease animal models related to bone regeneration, myocardial infarction, acute kidney injury, acute hepatic failure, skin injury, ischemic hind limb or cancer. The major aim of this review is to summarize the advent of hAFSCs capabilities into novel therapeutic modalities and discuss their potential use in future pre-clinical and clinical studies.

There is compelling evidence that mesenchymal stem cells (MSCs) can be utilized as delivery vehicles for cancer therapeutics. During the last decade, bone marrow MSCs have been used as delivery vehicles for the local production of therapeutic proteins in multiple tumor types, taking advantage of their innate tropism to the tumor site and their low immunogenicity. More recently, MSCs have been isolated from fetal tissues during gestation or after birth. Fetal MSCs derived from amniotic fluid, amniotic membrane, umbilical cord matrix (Wharton's jelly) and umbilical cord blood are more advantageous than adult MSCs, as they can be isolated noninvasively in large numbers without the ethical reservations associated with embryo research. Several studies have documented that fetal MSCs harbor a therapeutic potential in cancer treatment, as they can home to the tumor site and reduce tumor burden. This natural tumor tropism together with their low immunogenicity renders fetal MSCs as powerful therapeutic tools in gene therapy-based cancer therapeutic schemes. This review summarizes various approaches where the tumor-homing capacity of fetal MSCs has been employed for the localized delivery of anti-tumor therapeutic agents.

In recent years there seems to be an unbounded interest concerning mesenchymal stem cells (MSCs). This is mainly attributed to their exciting characteristics including long-term ex vivo proliferation, multilineage potential and immunomodulatory properties. In this regard MSCs emerge as attractive candidates for various therapeutic applications. MSCs were originally isolated from the bone marrow (BM) and this population is still considered as the gold standard for MSC applications. Nevertheless the BM has several limitations as source of MSCs, including MSC low frequency in this compartment, the painful isolation procedure and the decline in MSC characteristics with donor's age. Thus, there is accumulating interest in identifying alternative sources for MSCs. To this end MSCs obtained from the Wharton's Jelly (WJ) of umbilical cords (UC) have gained much attention over the last years since they can be easily isolated, without any ethical concerns, from a tissue which is discarded after birth. Furthermore WJ-derived MSCs represent a more primitive population than their adult counterparts, opening new perspectives for cell-based therapies. In this review we will at first give an overview of the biology of WJ-derived UC-MSCs. Then their potential application for the treatment of cancer and immune mediated disorders, such graft versus host disease (GVHD) and systemic lupus erythematosus (SLE) will be discussed, and finally their putative role as feeder layer for ex vivo hematopoietic stem cell (HSC) expansion will be pointed out.

The multilineage potentiality of cord blood stem cells has been experimentally proven in a number of cell based therapies. Umbilical cord blood (UCB) derived mesenchymal stem cells (MSCs), on prolonged exposure with Lascorbic acid have been successfully differentiated in to osteoblasts (bone forming cells) without altering the phenotype of the cells. In this case study, the role of L-ascorbic acid on collagen biosynthesis and mineral deposition in MSCs has been assessed, which are ultimately matured in to an insoluble extra cellular matrix (ECM), giving mechanical strength to the bone cells. Moreover, up to specific concentration of L-ascorbic acid (250μM), proliferation as well as differentiation potential of the cells remains unaltered. Further increase in concentrations of L-ascorbic acid (500 μM) reduced the cell proliferation and subsequently leads to morphological changes in the cultures. This may be due to an immature antioxidant defense system, which can be overcome by treating the cell cultures with antioxidants. Our final results conclude that Lascorbic acid has positive effect on the ostogenic differentiation of cord blood stem cells, and the concentration of ascorbic acid is vital in cell proliferation and differentiation.

Background: In the absence of a gold standard for hematopoietic progenitor counting, the intra-laboratory variation between commonly used strategies for progenitor assessment was compared. Methods and Materials: We used a pool of FITC-conjugated monoclonal antibodies (CD14, CD11b) and PE-CD34 to facilitate CD34 counting, excluding CD14+/CD11b+ bright cells. We compared this protocol with other common methodologies, such as the single-staining approach, known as the Milan method, and the ISHAGE multiparameter method. Results: We show that the CD14/CD11b protocol is a valid approach to progenitor cell counting. Though different methods give different results for progenitor cell counting, Lin's coefficient shows high concordance among flow cytometry counts but a substantial difference with colony- forming unit counts. Both the ISHAGE and CD14/CD11b protocol give higher counts than the Milan method. Moreover, on revising the ISHAGE analysis, we described a rare population of cells with the CD34+CD45neg phenotype, which could have an impact in CD34 counting. Conclusions: We have designed a valid alternative approach for hematopoietic progenitor cell counting, and we show that different methods give different results.

The object of this study is to evaluate the effects of injecting adult human bone marrow stromal cells (hBMSCs) into rats with severe traumatic brain injury in acute phase and to determine more optimal injection timing between day 1 and day 2 postinjury. The lateral fluid percussion injury model was used. Adult hBMSCs were transplanted into hemisphere to injury sites in the corpus callosum ipsilateral on day 1 (n = 12) or day 7 (n = 8) after injury. A control group (n = 7) underwent only a sham operation without stem cell transplantation. Rats in all groups were analyzed by magnetic resonance spectroscopy (MRS), and by using behavioral, rotarod, and Barnes maze tests on day 1, 7, 14, and 42. Another nine randomly designated rats were sacrificed for immunohistochemical staining. Behavioral test scores increased significantly at all time-points after TBI in the day 7-injected group, compared to the others (p=0.008). GFAP staining was lower on day 42 in day 7-injected rats than in those injected on day 1. But no significant inter- or intra-group differences were observed for other tests. The injection of hBMSCs was found to have limited therapeutic potential with respect to neuroprotection after traumatic brain injury. However, because injection on day 7 after TBI produced greater functional improvements in neurobehavioral tests and more effectively suppressed astroglial activation than an injection on post-injury day 1, we cautiously recommend the injection time of day 7 post injury in hBMSCs transplantation in severe TBI, rather than day 1 post injury but further studies on developing hBMSC-based new therapeutic approaches should be warranted for improving neuroprotection in severe TBI.