JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE REVIEW ARTICLE J Tissue Eng Regen Med 2008; 2: 169–183. Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/term.83 Updates on stem cells and their applications in regenerative medicine Stefan Bajada 1,2 *, Irena Mazakova 1,3 , James B. Richardson 1,2 and Nureddin Ashammakhi 1,2 1 Institute for Science and Technology in Medicine, Keele University, Staffordshire, UK 2 Institute of Orthopaedics, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, UK 3 Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, UK Abstract Stem cells have the capacity for self-renewal and capability of differentiation to various cell lineages. Thus, they represent an important building block for regenerative medicine and tissue engineering. These cells can be broadly classified into embryonic stem cells (ESCs) and non-embryonic or adult stem cells. ESCs have great potential but their use is still limited by several ethical and scientific considerations. The use of bone marrow-, umbilical cord-, adipose tissue-, skin- and amniotic fluid-derived mesenchymal stem cells might be an adequate alternative for translational practice. In particular, bone marrow-derived stem cells have been used successfully in the clinic for bone, cartilage, spinal cord, cardiac and bladder regeneration. Several preclinical experimental studies are under way for the application of stem cells in other conditions where current treatment options are inadequate. Stem cells can be used to improve healthcare by either augmenting the body’s own regenerative potential or developing new therapies. This review is not meant to be exhaustive but gives a brief outlook on the past, present and the future of stem cell-based therapies in clinical practice. Copyright  2008 John Wiley & Sons, Ltd. Received 8 November 2007; Revised 12 February 2008; Accepted 11 March 2008 Keywords stem cells; mesenchymal stem cells; clinical trials; tissue engineering; regenerative medicine; bone; skin-derived progenitor cells; fracture non-union 1. Introduction Regenerative medicine is an emerging and rapidly evolving field of research and therapeutics. Daar and Greenwood (2007) stated that regenerative medicine aims at ‘repair, replacement or regeneration of cells, tissue or organs to restore impaired function’. It aids the body to form new functional tissue to replace lost or defective tissue. Ultimately, this will help to provide therapeutic treatment for conditions where current therapies are inadequate. The human body has an endogenous system of regeneration and repair through stem cells, where stem cells can be found almost in every type of tissue. This process is highly evolved through evolution, and so it is logical that restoration of function is best accomplished by these cells. Therefore, stem cells hold great promise *Correspondence to: Stefan Bajada, Institute of Orthopaedics, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, UK. E-mail: stefan bajada@yahoo.com for the future of translational medicine. Despite much interest in stem cell biology, there are few examples of clinical applications to date. Possible explanations for this include: • Problems associated with extensive in vitro cell expan- sion. • Cell apoptosis following implantation (Vacanti, 2006). • Difficulties in obtaining vascularization (Griffith et al., 2005). • Problems with carrier biomaterials. • Moral concerns and ethical issues that hinder clinical translation. • Costs of prolonged cell culture. This review is not meant to be exhaustive, but aims to highlight present and future applications of stem cells in this exciting new discipline. We will briefly discuss tissue-engineering and stem-cell technology, including their different sources. Copyright  2008 John Wiley & Sons, Ltd.