Currents in Stem Cell Medicine
August 8, 2011. Volume 1, Number 1.

Welcome to the inaugural edition of Currents in Stem Cell Medicine. This is a bi-weekly bulletin from the International Cellular Medicine Society to keep you informed of the latest research and trends in stem cells. If there are areas of special interest that you would like the ICMS to include, please do not hesitate to contact us, and let us know. If you value this kind of independent, unbiased information, I urge you to join the ICMS, and to take a leadership role in defining the future of stem cell medicine.

Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes and pancreatic islets.
Cardinale et al. HEPATOLOGY (2011).
Multipotent stem/progenitors are present in peribiliary glands of extrahepatic biliary trees from humans of all ages and in high numbers in hepato-pancreatic common duct, cystic duct and hilum. The phenotypes and availability from all age donors suggest that these stem/progenitors have considerable potential for regenerative therapies of liver, bile duct and pancreatic diseases including diabetes.

Gene Expression Profiling Suggests a Pathological Role of Human Bone Marrow-Derived Mesenchymal Stem Cells in Aging-Related Skeletal Diseases.
Jiang et al. Aging (2011 Jul 28).
Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC) may play an important role. Collectively, the results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.

Hematopoietic stem and progenitor cell trafficking.Tissue engineering, regenerative medicine, and rejuvenation in 2010: the role of adipose-derived stem cells.
Beeson et al. Facial Plast Surg. (2011 Aug;27(4):378-88).
Facial rejuvenation is rapidly evolving sector in the field of facial aesthetics. This article reviews the history of soft tissue augmentation using adipose tissue grafting and the advent of using adipose-derived stem cells. The state-of-the-art stem cell isolation technique as well as anticipated future therapeutic indications are also addressed. 

Dedifferentiated fat cells: an alternative source of adult multipotent cells from the adipose tissues.
Shen JF et al. Int J Oral Sci. (2011 Jul;3(3):117-24).
When adipose-derived stem cells (ASCs) are retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dedifferentiated into lipid-free fibroblast-like cells, named dedifferentiated fat (DFAT) cells. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine. 

Bone Marrow Mesenchymal Cells: How Do They Contribute to Tissue Repair and Are They Really Stem Cells?
Kuroda et al. Arch Immunol Ther Exp (Warsz). (2011 Jul 26).
Adult stem cellstypically generate the cell types of the tissue in which they reside, and thus the range of their differentiation is considered limited. Bone marrow mesenchymal stem cells (MSCs) are different from other somatic stem cells in that they differentiate not only into the same mesodermal-lineage such as bone, cartilage, and adipocytes but also into other lineages of ectodermal and endodermal cells. This review summarizes recent advances in the clarification of MSC properties and discusses future perspectives. 

Perinatal sources of mesenchymal stem cells: Wharton's jelly, amnion and chorion.
Witkowska-Zimny et al. Cell Mol Biol Lett. (2011 Sep;16(3):493-514).  
Recently, stem cell biology has become an interesting topic, especially in the context of treating diseases and injuries using transplantation therapy. This review highlights the characteristics and therapeutic potential of three human mesenchymal stem cell types obtained from perinatal sources: Wharton's jelly, the amnion, and the chorion.

The simplest method for in vitro β-cell production from human adult stem cells.
Colin et al. Differentiation. (2011 Jul 20).
Diabetes mellitus is a challenging autoimmune disease. Biomedical researchers are currently exploring efficient and effective ways to solve this challenge. The methods investigated in this study can be considered an effective and efficient means of obtaining insulin-producing cells from adult stem cells within a week.

Autologous Transplantation of Adipose-Derived Mesenchymal Stem Cells Markedly Reduced Acute Ischemia-Reperfusion Lung Injury in a Rodent Model.
Sun et al. J Transl Med. (2011 Jul 22;9(1):118).
This study tested the hypothesis that autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) can effectively attenuate acute pulmonary ischemia-reperfusion (IR) injury. ADMSC therapy minimized lung damage after IR injury in a rodent model through suppressing oxidative stress and inflammatory reaction. 

Very Small Embryonic- like Stem Cells with Maximum Regenerative Potential get Discarded during Cord Blood Banking and Bone Marrow Processing for Autologous Stem Cell Therapy.
Bhartiya et al. Stem Cells Dev. (2011 Jul 22).
Very small embryonic-like stem cells (VSELs) are possibly lost during cord blood banking and bone marrow processing for autologus stem cell therapy mainly because of their small size. The results of the study presented may help explain low efficacy reported during adult autologous stem cell trials wherein unknowingly progenitor stem cells are injected rather than the pluripotent stem cells with maximum regenerative potential. 

Transplantation of adipose stromal cells promotes neovascularization of random skin flaps.
Sheng et al. Tohoku J Exp Med. (2011;224(3):229-34).
The delivery of bone marrow-derived mononulear cells (BM-MNCs) has been proved to be effective at promoting neovascularization of ischemic skin flaps. However, the limited source of BM-MNCs restricts their clinical application. Stromal vascular fraction (SVF) contains a group of heterogeneous cells in the adipose tissue, including adipose tissue-derived stem cells, and it has abundant reserve in human body. This study evaluates the therapeutic potential of SVF to promote neovascularization of random skin flaps. The results indicate that SVF could promote vascularization and increase flap survival probably by secreting VEGF and bFGF. The effect of transplantation of SVF on therapeutic angiogenesis of skin flaps is equivalent to that of BM-MNCs. 

Adipose-derived stromal cells: Their identity and uses in clinical trials, an update.
Casteilla et al. World J Stem Cells. (2011 Apr 26;3(4):25-33).
In adults, adipose tissue is abundant and can be easily sampled using liposuction. Largely involved in obesity and associated metabolic disorders, it is now described as a reservoir of immature stromal cells. These cells, called adipose-derived stromal cells (ADSCs) must be distinguished from the crude stromal vascular fraction (SVF) obtained after digestion of adipose tissue. ADSCs share many features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but they also display some specific features, including a greater angiogenic potential. Their angiogenic properties as well as their paracrine activity suggest a putative tumor-promoting role for ADSCs although contradictory data have been published on this issue. Both SVF cells and ADSCs are currently being investigated in clinical trials in several fields (chronic inflammation, ischemic diseases, etc.). Apart from a phase III trial on the treatment of fistula, most of these are in phase I and use autologous cells. In the near future, the end results of these trials should provide a great deal of data on the safety of ADSC use. 

Engineering of large osteogenic grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose tissue.
Güven et al. Biomaterials. (2011 Sep;32(25):5801-9. Epub 2011 May 24).
This study investigated whether the maintenance in culture of endothelial and mesenchymal progenitors from the stromal vascular fraction (SVF) of human adipose tissue supports the formation of vascular structures in vitro and thereby improves the efficiency and uniformity of bone tissue formation in vivo within critically sized scaffolds. As compared to BMSC and ASC, SVF-derived cells promoted faster tissue ingrowth, more abundant and uniform bone tissue formation, with ossicles reaching a 3.5 mm depth from the scaffold periphery after 8 weeks. Our findings demonstrate that maintenance of endothelial/mesenchymal SVF cell fractions is crucial to generate osteogenic constructs with enhanced engraftment capacity. The single, easily accessible cell source and streamlined, bioreactor-based process makes the approach attractive towards manufacturing of clinically relevant sized bone substitute grafts. 

Clinical trial of autologous differentiated adipocytes from stem cells derived from human adipose tissue.
Kim et al. Dermatol Surg. (2011 Jun;37(6):750-9).
Adipose tissue-derived stem cells (ASCs) are considered to be a reliable cell source for the generation of adipose tissue because they can be differentiated into adipocytes. Previous data have indicated that adipogenic differentiation of ASCs before transplantation can enhance the regeneration of adipose tissue. This study was intended to evaluate the efficacy and safety of the use of autologous differentiated adipocytes for the treatment of depressed scars. The conclusion of the study is that the use of autologous differentiated adipocytes can be a safe and effective treatment for soft tissue defects, with relatively long-term maintenance of volume. The authors have indicated no significant interest with commercial supporters.

Safety of autologous bone marrow aspiration concentrate transplantation: initial experiences in 101 patients.
Hendrich et al. Orthop Rev (Pavia). (2009 Oct 10;1(2):e32).
The clinical application of cellular based therapies with ex vivo cultivation for the treatment of diseases of the musculoskeletal system has until now been limited. In particular, the advanced laboratory and technical effort necessary, regulatory issues as well as high costs are major obstacles. On the other hand, newly developed cell therapy systems permit intra-operative enrichment and application of mesenchymal and progenitor stem cells from bone marrow aspirate concentrate (BMAC) in one single operative session. The objective of the present clinical surveillance study was to evaluate new bone formation after the application of BMAC as well as to record any possible therapy-specific complications. In the authors' opinion, the on-site preparation of the bone marrow cells within the operating theater eliminates the specific risk of ex vivo cell proliferation and has a safety advantage in the use of autologous cell therapy for bone regeneration. 

Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells.
Hung et al. J Orthop Res. (2011 Aug 1).
Mesenchymal stem cells(MSCs), which can be isolated from bone marrow and other somatic tissues, are residing in an environment with relative low oxygen tension. The purpose of this study is to investigate the effects of hypoxia on MSCs. The authors hypothesize that oxygen concentration regulates the intricate balance between cellular proliferation and commitment towards differentiation. The conclusion of this study is that hypoxia provides a favorable culture condition to promote proliferation as well as osteogenesis of MSCs through differential growth factor production. 

Mesenchymal stem cells derived from Wharton jelly of the human umbilical cord ameliorate damage to human endometrial stromal cells.
Yang et al. Fertil Steril. (2011 Jul 29).
The purpose of this study is to investigate the effect of mesenchymal stem cells isolated from Wharton jelly of umbilical cord (WJ-MSCs) on ameliorating damaged human endometrial stromal cells (ESCs).Sixteen endometrial tissues were obtained from women undergoing hysterectomy. Eight umbilical cords were obtained from full-term deliveries.
After exposure to mifepristone, the proliferation of ESCs decreased and the apoptosis percentage increased in a dose- and time-dependent manner. At a certain dose and duration, this damage continued even after the withdrawl of mifepristone at 48 hours. When the damaged ESCs were cocultured with WJ-MSCs, the proliferation of these damaged cells was significantly increased and apoptosis percentage decreased. In addition, the level of VEGF mRNA and protein decreased and that of caspases 3, 8, and 9 increased. WJ-MSCs may serve as a promising treatment approach to ameliorate endometrial damage.