Regenerative Medicine

Publications in this journal

• Article: Is urine the next source of stem cells?

  Leann Crandall, Marc Lalande
  Regenerative Medicine 05/2013; 8(3):235-6.
• Article: Transient overexpression of Pparγ2 and C/ebpα in mesenchymal stem cells induces brown adipose tissue formation.

  Dmitriy Sheyn, Gadi Pelled, Wafa Tawackoli, Susan Su, Shiran Ben-David, Dan Gazit, Zulma Gazit
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  ABSTRACT: Background: Brown adipose tissue plays a pivotal role in mammal metabolism and thermogenesis. It has a great therapeutic potential in several metabolic disorders such as obesity and diabetes. Mesenchymal stem cells (MSCs) are suitable candidates for brown adipose tissue formation de novo. Pparγ2 and C/ebpα are nucleic receptors known to mediate adipogenic differentiation. We hypothesized that overexpression of the Pparγ2 and C/ebpα genes in MSCs would lead to the formation of adipose tissue. Materials & methods: MSCs bearing the Luc reporter gene were transfected to overexpress Pparγ2 and C/ebpα. Differentiation of nucleofected cells was evaluated in vitro and in vivo following ectopic implantation of the cells in C3H/HeN mice. Results: After implantation, the engineered cells survived for 5 weeks and brown adipose-like tissue was observed in histological samples. Immunostaining and bioluminescent imaging showed new adipocytes expressing Luc and the brown adipose tissue marker, UCP1, in vitro and in vivo. Conclusion: We show that gene delivery of transcription factors into MSCs generates brown adipose tissue in vitro and in vivo.
  Regenerative Medicine 05/2013; 8(3):295-308.
• Article: Interview: The commercialization of regenerative medicine into a routine healthcare offering.

  Robert Deans
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  ABSTRACT: Robert Deans speaks to Alexandra Hemsley, Commissioning Editor Robert Deans has led Athersys Inc.'s (OH, USA) regenerative medicine research and development activities since February 2003 and has served as Vice President of Regenerative Medicine since October 2003. He was named Executive Vice President of Regenerative Medicine in April 2011. Deans is highly regarded as an expert in stem cell therapeutics, with over 20 years of experience in this field. From 2001 to 2003, Deans worked for early-stage biotechnology companies. Deans was formerly the Vice President of Research at Osiris Therapeutics, Inc. (MD, USA), a biotechnology company, from 1998 to 2001 and Director of Research and Development with the Immunotherapy Division of Baxter International, Inc. (IL, USA), a global healthcare company, from 1992 to 1998. Deans was also previously on the faculty at University of Southern California Medical School in Los Angeles (CA, USA) between 1981 and 1998, in the departments of microbiology and neurology at the Norris Comprehensive Cancer Center. Deans was an undergraduate at Massachusetts Institute of Technology, received his PhD at the University of Michigan and did his post-doctoral work at University of California in Los Angeles, CA, USA. Aside from his Athersys responsibilities, Deans has a very active role within the International Society for Cellular therapy, specifically in Chairing the Commercialization Committee, and the Alliance for Regenerative Medicine, where he is co-chair of the Science and Technology committee.
  Regenerative Medicine 05/2013; 8(3):251-6.
• Article: Limbal side population cells: a future treatment for limbal stem cell deficiency.

  Bakiah Shaharuddin, Sajjad Ahmad, Simi Ali, Annette Meeson
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  ABSTRACT: Corneal blindness carries a morbidity that affects quality of life and is often associated with an increased economic burden. In this review, we focus on the severe and painful condition of limbal stem cell deficiency, an important cause of corneal blindness. Conventional corneal transplantation usually results in graft failure and is contraindicated in this condition. Ex vivo-expanded limbal epithelial transplantation has been used as a cellular-based therapy to regenerate and reconstruct the ocular surface as a mode of treatment. Enrichment methods for stem cells are a strategy to improve the outcome of limbal stem cell transplantation. Here we discuss the side population assay as a functional assay to enrich for stem cells as an important source of limbal stem cells. The challenges in ex vivo-expanded limbal stem cell transplantation are wide and varied and will be addressed in this review with regard to improving the clinical outcomes of cultivated limbal stem cell transplantation.
  Regenerative Medicine 05/2013; 8(3):319-31.
• Article: Bidirectional and mutually beneficial interactions between human mesenchymal stem cells and osteoarthritic chondrocytes in micromass co-cultures.

  Hua Jia Diao, Chui Wai Yeung, Chun Hoi Yan, Godfrey Cf Chan, Barbara P Chan
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  ABSTRACT: Aim: Mesenchymal stem cell (MSC)-based therapy presents a promising approach for treating osteoarthritis (OA). However, the molecular interactions between MSCs and OA chondrocytes (OACs) are not known. This study aims to investigate the bidirectional interactions between human MSCs (hMSCs) and human OACs (hOACs) in a 3D co-culture system. Materials & methods: hMSC-collagen microspheres were cultured in hOAC-conditioned medium or co-cultured with hOAC-collagen microspheres. Growth characteristics, glycosaminoglycan (GAG) production, gene expression of major OA-associated chondrogenic markers, including SOX9, COL2A1, ACAN and MMP13, were investigated in both cell types. Results: Both the conditioned medium and the co-culture induced MSC chondrogenesis with enhanced GAG production, SOX9 gene and protein expression, and gene expression of ACAN and COL2A1. Meanwhile, the co-culture also induced hOACs to partially resume the lost chondrogenic phenotype as shown by reduced proliferation, enhanced GAG production when hMSCs were chondrogenically predifferentiated, and reduced MMP13 gene expression. Conclusion: This work suggests that 3D co-culture of hMSCs and hOACs is mutually beneficial to each other, suggesting the potential therapeutic effect of delivering hMSC in scaffolds directly to OA defects.
  Regenerative Medicine 05/2013; 8(3):257-69.
• Article: Bioengineering of articular cartilage: past, present and future.

  Ken Ye, Raed Felimban, Simon E Moulton, Gordon G Wallace, Claudia Di Bella, Kathy Traianedes, Peter Fm Choong, Damian E Myers
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  ABSTRACT: The treatment of cartilage defects poses a clinical challenge owing to the lack of intrinsic regenerative capacity of cartilage. The use of tissue engineering techniques to bioengineer articular cartilage is promising and may hold the key to the successful regeneration of cartilage tissue. Natural and synthetic biomaterials have been used to recreate the microarchitecture of articular cartilage through multilayered biomimetic scaffolds. Acellular scaffolds preserve the microarchitecture of articular cartilage through a process of decellularization of biological tissue. Although promising, this technique often results in poor biomechanical strength of the graft. However, biomechanical strength could be improved if biomaterials could be incorporated back into the decellularized tissue to overcome this limitation.
  Regenerative Medicine 05/2013; 8(3):333-49.
• Article: The potential of stem cells for the restoration of auditory function in humans.

  Zhengqing Hu, Mats Ulfendahl
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  ABSTRACT: Hearing loss is one of the most common disabilities, affecting approximately 10% of the population. Hair cells and spiral ganglion neurons are usually damaged in most cases of hearing loss. Currently, there is virtually no biological approach to replace damaged hearing cells. Recent developments in stem cell technology provide new opportunities for the treatment of deafness. Two major strategies have been investigated: differentiation of endogenous stem cells into new hair cells; and introduction of exogenous cells into the inner ear to substitute injured hearing neurons. Although there is still a learning curve in stem cell-based replacement, the probability exists to utilize personalized stem cells to eventually provide a novel intervention for patients with deafness in future clinical research trials.
  Regenerative Medicine 05/2013; 8(3):309-18.
• Article: Human umbilical cord blood stem cells for spinal cord injury: early transplantation results in better local angiogenesis.

  Guangzhi Ning, Liang Tang, Qiang Wu, Yulin Li, Yan Li, Chao Zhang, Shiqing Feng
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  ABSTRACT: Aim: We aim to explore the repair mechanism after the transplantation of CD34(+) human umbilical cord blood cells (HUCBCs) in traumatic spinal cord injury (SCI) in rats. Materials & methods: Wistar rats with SCI were randomly divided into three groups: DMEM injection (group A); CD34(+) HUCBC transplantation on the first day after injury (group B); and CD34(+) HUCBC transplantation on the sixth day after injury (group C). The Basso, Beattie and Bresnahan scores were used to evaluate motor behavior. At the injured site, the infarct size, blood vessel density, and survival and neural differentiation of transplanted cells were analyzed. Results: It was found that the Basso, Beattie and Bresnahan score in group B was significantly higher than other groups (p < 0.05), and the infarct size and blood vessel density at the injured site were significantly different (p < 0.01). However, the transplanted cells survived at least 3 weeks at the injured site, but did not differentiate into neural cells. Conclusion: These results suggested transplantation of CD34(+) HUCBCs during the acute phase could promote the functional recovery better than during the subacute phase after SCI by raising blood vessel density, suggesting the possible clinical application for the treatment of spinal injury.
  Regenerative Medicine 05/2013; 8(3):271-81.
• Article: Reassessing direct-to-consumer portrayals of unproven stem cell therapies: is it getting better?

  Ubaka Ogbogu, Christen Rachul, Timothy Caulfield
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  ABSTRACT: Aim: To determine whether increased scrutiny of 'stem cell tourism' has resulted in changes to online claims by clinics that provide putative unproven stem cell treatments. Materials & methods: We analyzed historical and current versions of clinics' websites. The study sample consisted of 18 websites included in a 2008 peer-reviewed study and an additional 12 clinics identified through the Google™ search engine. Results: Our analysis revealed similarities between historical and current stem cell treatment offerings, claims, representations of risk, benefit and efficacy and attention to social, ethical and regulatory concerns. Claims and representations remain overly optimistic. Current websites provide more detailed descriptions of treatment procedures and outcomes and are more aesthetically appealing. Noteworthy trends in the movements and locations of clinics was observed. Conclusion: Increased scrutiny of stem cell tourism has not had much impact on the online claims of clinics that provide putative unproven stem cell treatments.
  Regenerative Medicine 05/2013; 8(3):361-9.
• Article: Potentiated therapeutic angiogenesis by primed human mesenchymal stem cells in a mouse model of hindlimb ischemia.

  Eun Ju Lee, Hwan-Woo Park, Hyo-Jin Jeon, Hyo-Soo Kim, Mi-Sook Chang
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  ABSTRACT: Background: Human bone marrow-derived mesenchymal stem cells (hMSCs) are advantageous for cell-based therapy to treat ischemic diseases owing to their capacity to secrete various paracrine factors with potent angiogenic activity. Materials & methods: In this study, we describe a method to increase secreted levels of VEGF and HGF from hMSCs without genetic modification. Results: We demonstrated that transplantation of primed hMSCs into ischemic limbs led to significantly greater improvements in tissue perfusion and limb salvage by increasing capillary formation compared with nonprimed hMSCs. The primed hMSCs also exhibited greater survival in vivo and secreted human VEGF and HGF in the ischemic tissue, supporting enhanced angiogenesis and cell survival. Conclusion: These findings indicate that priming hMSCs via methods described in this study enhances secretion of critical proangiogenic factors resulting in an enhanced therapeutic effect of cells for the treatment of ischemic diseases.
  Regenerative Medicine 05/2013; 8(3):283-93.
• Article: Regenerative medicine techniques in cardiovascular disease: where is the horizon?

  Claire Packer, Beth Boddice, Sue Simpson
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  ABSTRACT: Regenerative medicine techniques to restore cardiac and vascular function are being increasingly investigated as management options for cardiovascular disease. The authors set out to identify emerging regenerative techniques in cardiovascular disease and investigate their stage of development. The relevant networks in the field in the UK were contacted and online sources for cell therapy, tissue engineering, and other regenerative techniques and products were searched for online. A total of 49 Phase II, II/III and III trials of regenerative products or techniques were identified: 13 Phase III, eight Phase II/III and 28 Phase II trials. Twelve of the Phase III trials are for myocardial ischemia and involve an intracoronary infusion or intramyocardial injection of autologous bone marrow-derived stem cells. Most of those in Phase III trials are, however, associated either with an unproven delivery technique or cellular approach. The authors conclude that translation into clinical practice and diffusion into health systems is some way off.
  Regenerative Medicine 05/2013; 8(3):351-60.
• Article: Strategies of human corneal endothelial tissue regeneration.

  Alfonso L Sabater, Adriano Guarnieri, Edgar M Espana, Wei Li, Felipe Prósper, Javier Moreno-Montañés
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  ABSTRACT: Penetrating keratoplasty has previously been the only surgical treatment for patients with corneal endothelial disorders. Recently, posterior lamellar keratoplasty has become a viable and less aggressive alternative technique. However, both transplantation techniques have disadvantages, such as non-immunologic graft failure, allograft endothelial rejection or a global shortage of donor corneas. Over the past few years, several groups have established methods for the isolation, preservation, in vitro cultivation, transplantation, and in vivo stimulation of human corneal endothelial cells in animal models. It is hoped that these new strategies will allow the treatment of more than one patient with one donor cornea, performing autologous corneal endothelium transplantation from a surgical biopsy sample, or stimulating the growth of corneal endothelial cells in vivo. However, several aspects need to be addressed before commencing clinical trials.
  Regenerative Medicine 03/2013; 8(2):183-95.
• Article: Understanding regenerative medicine: a commissioner's viewpoint.

  Virginia Warren
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  ABSTRACT: Regenerative medicines (RMs) represent a relatively new mode of care. Commissioners of healthcare need a pragmatic method to identify RMs which are safe and that will, when delivered in the context of an appropriate care pathway, avoid premature death and reduce morbidity for patients. This article offers a way of distinguishing between those which are useful currently and those which are not, although they may be in the future. This information is set in the context of reflection on issues that experience has demonstrated to be relevant to funding RMs. This article is potentially useful to developers of RM products as well as to commissioners of care, as it demonstrates what information will be required for a key step towards the adoption of their product.
  Regenerative Medicine 03/2013; 8(2):227-32.
• Article: Oxygen-controlled automated neural differentiation of mouse embryonic stem cells.

  Paul Mondragon-Teran, Rui Tostoes, Chris Mason, Gary J Lye, Farlan S Veraitch
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  ABSTRACT: Automation and oxygen tension control are two tools that provide significant improvements to the reproducibility and efficiency of stem cell production processes. Aim: the aim of this study was to establish a novel automation platform capable of controlling oxygen tension during both the cell-culture and liquid-handling steps of neural differentiation processes. Materials & methods: We built a bespoke automation platform, which enclosed a liquid-handling platform in a sterile, oxygen-controlled environment. An airtight connection was used to transfer cell culture plates to and from an automated oxygen-controlled incubator. Results: Our results demonstrate that our system yielded comparable cell numbers, viabilities, metabolism profiles and differentiation efficiencies when compared with traditional manual processes. Interestingly, eliminating exposure to ambient conditions during the liquid-handling stage resulted in significant improvements in the yield of MAP2-positive neural cells, indicating that this level of control can improve differentiation processes. Conclusion: This article describes, for the first time, an automation platform capable of maintaining oxygen tension control during both the cell-culture and liquid-handling stages of a 2D embryonic stem cell differentiation process.
  Regenerative Medicine 03/2013; 8(2):171-82.
• Article: Intravascular cell therapy in stroke patients: where the cells go and what they do.

  Matti Korhonen, Jukka Jolkkonen
  Regenerative Medicine 03/2013; 8(2):93-5.
• Article: Grounding the satellite turns on the signal.

  Eleftherios Sachlos
  Regenerative Medicine 03/2013; 8(2):119-20.
• Article: Call for fellowship programs in stem cell-based regenerative and cellular medicine: new stem cell training is essential for physicians.

  Paul S Knoepfler
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  ABSTRACT: Stem cell-based regenerative and cellular medicine is an exciting, emerging area of medical practice. While bone marrow transplantation, a stem cell-based therapy, has been a part of medicine for decades, in recent years newer and more diverse forms of stem cell-based therapies are being used to treat a rapidly growing population of patients in the USA as well as worldwide. Nonetheless, to this author's knowledge, there is currently not a single academic medical fellowship training program in the USA that specifically prepares physicians for treating patients with stem cell-based therapies other than bone marrow or hematopoietic stem cell transplantation. An increasing number of physicians untrained in stem cell-based regenerative and cellular medicine are nonetheless transplanting stem cells into hundreds if not thousands of patients for a striking diversity of conditions. Furthermore, as stem cell technology advances, a growing number of physicians with academic affiliations may look to legitimately practice regenerative and cellular medicine. What little training that physicians can currently obtain must be found on an ad hoc basis. This article should act as a call for the development of formal academic medical fellowship programs to train physicians in the practice of cellular and regenerative medicine. The USA is used here as an example of a medical sphere in which it can be argued that such training would be helpful, however such programs would be quite helpful globally.
  Regenerative Medicine 03/2013; 8(2):223-5.
• Article: Cardiac regeneration based on pharmacologic control of the cardiac autonomic system.

  Paolo Madeddu
  Regenerative Medicine 03/2013; 8(2):118-9.