Unlocking the potential of adult stem cells ‘We now expect to live longer and hope to achieve this along with a good quality of life. However, we are starting to outlive the useful life of many of our tissues and organs. This article shows how the ability of stem cells to grow on novel materials could help us to develop replacemnent tissues, Panes) Uupportive tissues such as bone and cartilage ‘may become damaged or diseased with age. por Orthopaedic surgeons can use replacement parts but these have a limited lifespan and repeat rephcement surgery is complex and risky For degenerative neurological diseates, such as Parkinsons and Alzheimers, there is no replacement ‘option. One solution to these problems may i with the use of stem cll, "Embryonic stem cells have been the headline grabbers in thestem cell world. They are pluripotent, ‘meaning they can make any cll type in the body = +0 potentially could be a source of replacement tissue, However their use fs ethially aid eglly Semele Ortnopaesies omterais Teste engneerng challenging. Religious groups are divided on when fn embryo becomes ‘person’ Some argue that this hhappens at conception and this embryonic stem cells should not be used for research and medicine (Others argue fora later point — for example. when 4 noticeable nervous system has formed [reek 3 of embryonic development) — and thatitis fine to use the stem cells before this time, Such debates have limited embryonic stem cll research, stimulating scientists to ook for aernatvesoures of tem cells (ur adulthodies also have tem cells These adult stem cells respond todamage and disease, becoming ‘tivated when needed, They are mukipotent — ie ‘hey can only form a limited range of tnsues. For logical Scenes Reviewcxample, mesenchysnal stm cells can form bone carclage, ligament and tendon and are found inthe bhone marrow. When an orthopaedie surgeon does a hip nl ana the stem cls isolated. There is anther pe of sem cel in bone marrow called the haematopoietic A blood ‘multipotent stem cel, The bone marrow is the cement, the bone marrow can bere stem cell ells are derived from this Known source of stem cells in the adult, and bone ‘marrow stem cell herapyhas been used for decades Bone mattow transplants ace used (0 inttoduce haematopoietic stem cells from healthy dono nto leukaemia patents after their own diseased stem cellshave been irradisted and therefore billed ‘Tissue engineering The presence of multipotent stem cells in our bodies throughout our lives means tha they could potentially be used to replace damaged or defective Usaues, However, todo this we must find a way 0 rowing these cells outside out body, because there are insfficient numbers ofthese cells fom sources chas the bone marrow to form replacement tissue owth or caltaring of stem ells i esental If we ate 1 unlock their potential. Culturing cells ‘outsdethe body is justthe startf the proces. Once suficient numbers of cell have been established by culturing, they then need to differentiate nko cells that will ukimately form specific tissu, For example, mesenchymal cells can potential iferentatevo form bone, gamentor tendon in the laboratory, jst as they do inthe body. The process of differentiating cells within material seaffalds ‘outside the Body ~ so that thy form speci tisues that can be reintrodueed ino the body ~ is often fefeted 10 as tase engineering, The ultimate goal of tissue engineers isto guow ‘ofthe shell” tissue organs fom cell and aymthetic materials chat can be used a required, So far ssue engineering has found success in a small number of applications such as cartilage repair, bladder and trachea replacement. n each of these cass, cells have been isolated from patients and grown on materials inthe laboratory before being put back into the patent. Howevet, these are simple tissues where use of differentiated cells istine. Form re comple tissues, stem cells ate an strate alternative 10 use as replacement cells because they cam develop into tases thanks other ‘When stem cells ate put ito the body they are not very good at surviving, and often die because they do not adhere 40 the existing tisve cell death limits their potential use. The support imaterials used in Ussue engineering alow the eels to grow and survive when placed back into the This body. The materials used ate, ideally, biodegradable s0 that asthe cells start to do ther job inthe ort 2008 the material disappears and natural, healthy issue replaces it ‘Stem cells are hard to culture outside the body because they tend to differentiate quickly into diferent cell types. So, as well as being. able t0 discover materials that support giowth and allow iable implantation (the scaffolds), we also need (find materials that will allow us to grow enough high-quality (multipotent) stem cells populate he scafod Novel materials for stem cell culturing To culture and grow stem cells we need anderstand what normally triggers differentiation and prevent thi rom happening. How cells nteract with ey factor to take into Consideration, In the bods, proteins on the surface their environment ‘of stem cells wil attach to other cell orto a protein ‘caffold to maintain their undifferentiated status [bee Figure 1) We don’t know exactly how these interactions maintain stem cell mulkpotency but te do know that we can prevent stem cell from Aiflerentiting by culturing them on specialised materials, These materials ane manufactured to have specialised paternson ther surface. Certain patterns have been found to prevent the differentiation of stem cells enabling culturing and growth of large numbers of mescnehymal stem cells, The patterns are extemely small, cven smaller than the stem cells Tis manotopography i thought 10 mimic the natural environment ofthe tem cells in the body ‘Ourabilityo design pattens on material surface ‘comes from the computer industry. The latestare ea 10 Figure 3 Xray ofa total ip replace ofthe femora supports the new femoral head (the ‘all. inthis image, the Socket" has also been replaced vi 24 64 cart of SOO Udoo Figure 2 Composite image of mesenchymal stem clls ‘rewing on material with nanoscale patterns. On the highly erdered pattern towards the top, the stem cells do not differentiate On the disordered pattern tomards the bottom, the cel diferentat int eteablste Nile sre stained blue Cell mages by light mieoecop, material image by canning election microscopy. If the (would ecualy cover thousends of pts, Mesenchymal ‘tem els can spread up to approximately 200 pm long (around 1000 pte on ‘Along metal rod into the bone marrow computer microchips have been created throw election beam lithography. This uses focused electrons to write patterns on silicon. Engineers ‘an write patterns down 10 10 nanometes i size, ‘enabling the growth of ellson differently patterned snfaces to be analyse fn Glasgow, cell biologists and electronic engineers have joined forces to make these nanoscale patterns fr stem cll ‘Anexampl ofa pater thatcontolsmesenchyrmal stem cell self enewal sshoven in Figure 2 op). The Daaterns promote symmetrical cell division — so ‘we can now grow large numbers of multipetent stem cells This allows new possibilities for clinical stem cell use, such atin osteoporosis, Here stem cells capable of forming bone could compere with the bone absorbing activity of osteoclasts that in ‘osteoporosis areeveractive and weaken bones These novel patterned material surfaces can also be used to direct stem cell fate, As well as ‘controlling non-differentiated cell growth, targeted differentiation of sem cells desirable if you want to engineer + partcilat tise. By altering the degree of onder in which we arrange patterns, we ‘an contral the differentiation of mesenchymal stem cells to form bone (se Figure 2, bottom) Intriguingly. the optimal pattern resembles atype of collagen praduced by cll turing fom cartilage to eee! Adit stom cells Ste el ound ait They have ted iferenttion potenti ond are termed Biomimetic Minctng nature to gets postive Doig sponse Culture a einige used or growing heen ces couse te bod in aboratry conden. Embryonic stm cells Ear stage stem cals that «form any ts of he bad. Tey sre plriptet Nanotopography Shapes ss tan 200" in ie (iam = 10°. Osteoporosis Osgenerave conston where bore resorption ishighe than bone fermion Scaffold in tssve engineering a scat 3 material used support al growth, Stem ells Inmate esha can for uetorl col ps. ete ay Cldershavy R21 ‘Stem ls: new els foro, Bseoon Sorc Riven, ol 23, No gp. 22-25 hupsenikipedia rgwikiTissue engineering werwenanocrg.t sworwakectorg! wa stemcells org.uk logical Scenes Reviewbone. So thete seems to be a biomimetic rationale for histesponse, Siem ces on this surface also have Increased adhesion and this appeats 1 be the first sep in the bone formation proces. ngineers at Glasgow ate now striving t© put these patterns onto orthopaedic implant materials. ‘When a surgeon replaces a Tead-beating joint such 8-4 hip, they place a metal rod into your bone marrow to aecute the new joint (ee Tigute 3) However the rod does not stimulate your bone smartow mesenchymal stem cls w form bone — and, instead, soft, flbrous tissue forms. This leads to movement of the implant as dhe patient walks ‘This movement increases with time and this is one reason why such implants last only 10-15 years. IF we can pattern the materials to stimulate he stem cells t form bone, we could make implants that could lst lifetime ‘We can now envisage making complex tissue engineering safflds containing epions for self renewal and areas of targeted differentiation Challenges remain for engineers to make these patterns in thee-dimensional material frbiologsts to fill with cells inthe laboratory, and clinicians to node to areas in need of regeneration, We know that implanted neural stem cells survive much better if delivered in tissue engineering scaffolds than if just injected into a damaged area, sit also appears HODDER Getting the most from your magazine? Use the free online resources Register today fo re revision exoreses, weblinks, podcasts and lots more linked tothe artes in each issue. * Goin www.philipalian.co.uk/magazinesontine # Rogitor your dota with autor rae and password of your choice 1 Login win your code and keyword trom the back cover of Hisissue ‘that materials can offer a supporting role in stem «ell survival. One day te curtent research on novel ‘materials for culturing tem cells may result in new ‘replacement tissues that wil improve ur quality of life during old age. cart paged * stem eels canbe maniated to ge ested responses of prolonged grow nd ogee bone fomaton by nanoscale topography. ‘= Nanoscale pograply coud be used tmake new “mpl whee bane grout is estab. 1 We mater coud be used in isu engneetng where patent derive els are requred for engineering of sss in the laboratory before repiang deste o damaged tees the ecology eda be used t scale wp ol roductn to grew large numbers ft cl or ee in sue engine magazinesonline Subscribe to the online archives ‘Subseritions othe onine archives of back issues are avaliable for al our ‘level magazines. 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