DOCSLIB.ORG

Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development Curr Stem Cell Rep DOI 10.1007/s40778-016-0053-5 STEM CELLS: POLICIES FROM THE BENCH TO THE CLINIC (AI CAPLAN AND TL BONFIELD, SECTION EDITORS) Adipose Tissue and Mesenchymal Stem Cells: State of the Art and Lipogems® Technology Development Carlo Tremolada1 & Valeria Colombo 1 & Carlo Ventura2 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract In the past few years, interest in adipose tissue as an Lipogems® product, pericytes are retained within an intact ideal source of mesenchymal stem cells (MSCs) has in- stromal vascular niche and are ready to interact with the re- creased. These cells are multipotent and may differentiate cipient tissue after transplantation, thereby becoming MSCs in vitro into several cellular lineages, such as adipocytes, and starting the regenerative process. Lipogems® has been chondrocytes, osteoblasts, and myoblasts. In addition, they used in more than 7000 patients worldwide in aesthetic med- secrete many bioactive molecules and thus are considered icine and surgery, as well as in orthopedic and general surgery, Bmini-drugstores.^ MSCs are being used increasingly for with remarkable and promising results and seemingly no many clinical applications, such as orthopedic, plastic, and drawbacks. Now, several clinical trials are under way to sup- reconstructive surgery. Adipose-derived MSCs are routinely port the initial encouraging outcomes. Lipogems® technology obtained enzymatically from fat lipoaspirate as SVF and/or is emerging as a valid intraoperative system to obtain an opti- may undergo prolonged ex vivo expansion, with significant mal final product that may be used immediately for regenera- senescence and a decrease in multipotency, leading to unsat- tive purposes. isfactory clinical results. Moreover, these techniques are ham- pered by complex regulatory issues. Therefore, an innovative Keywords Mesenchymal stem cell . Lipogems® . Adipose technique (Lipogems®; Lipogems International SpA, Milan, tissue . Regenerative medicine . Adipose tissue-derived Italy) was developed to obtain microfragmented adipose tis- mesenchymal stem cell . Adult stem cells sue with an intact stromal vascular niche and MSCs with a high regenerative capacity. The Lipogems® technology, pat- ented in 2010 and clinically available since 2013, is an easy- Introduction to-use system designed to harvest, process, and inject refined fat tissue and is characterized by optimal handling ability and More than a century has passed since the first definition of a great regenerative potential based on adipose-derived stem cells as ancestral cells of the germ line [1], and since MSCs. In this novel technology, the adipose tissue is washed, then, a significant number of studies and discoveries emulsified, and rinsed and adipose cluster dimensions gradu- concerning their potential and application in regenerative ally are reduced to about 0.3 to 0.8 mm. In the resulting medicine and surgery have been published. In particular, more than 40,000 articles may be found on Medline by searching This article is part of the Topical Collection on Stem Cells: Policies from for human adult mesenchymal stem cells (MSCs) derived the Bench to the Clinic from bone marrow, dental pulp, fetal membrane, and term placenta. In vitro and in vivo experimental studies have dem- * Carlo Tremolada onstrated that human MSCs may differentiate in vitro into [email protected] several cell lineages, such as osteoblasts, chondrocytes, myocytes, and adipocytes [2]. 1 Image Institute, Milan, Italy In the past 15 years, it has been shown that human MSCs 2 Stem Wave Institute for Tissue Healing (SWITH)—Ettore Sansavini also can promote vasculogenesis, the main mechanism in- Health Science Foundation, Lugo, Ravenna, Italy volved in tissue repair effectiveness, cardiovascular Curr Stem Cell Rep differentiation, and myocardial repair [3], and have improved Bmedicinal signaling cells^ that can receive signals of in- islet graft revascularization in diabetic rats, enhancing engraft- jury from the environment and then respond by secreting ment success [4]. All the aforementioned discoveries inspired the appropriate molecules [22]. Dental pulp is considered the studies regarding Lipogems® (Lipogems International an effective MSC source for orthopedic and maxillofacial SpA, Milan, Italy) technology. reconstructions, because these MSCs can generate miner- Attention increasingly is being focused on MSCs de- alized tissue, extracellular matrix, and other connective rived from human and animal adipose tissue because of tissue, such as dentine, dental pulp, and periodontal liga- their abundance and ease of access. These multipotent ment [23].AlthoughMSCsclearlymaybeusedtoregen- cells can differentiate into mature adipocytes as well as erate the dental pulp itself [24, 25]andmayalsoinfluence chondrocytes, osteoblasts, myocytes, hepatocytes, the pathogenic pathways of some chronic brain and gut neuronal-like and endothelial cells, and other lineages, diseases (e.g., Parkinson’s and Alzheimer’s) [26], a treat- as suggested by in vitro, ex vivo, and in vivo evidence ment based on these cells is not yet available. Indeed, [5–14], and this potential may be used to regenerate dam- evidence obtained so far has been gathered only by using aged tissues. In addition, MSCs secrete a variety of bio- nonhuman xenotransplants and in vitro models. Bone active molecules that act in a paracrine fashion to prime marrow-derived MSCs also have been studied extensively and sustain angiogenic, antifibrotic, antiapoptotic, and im- for their great regeneration capability and their immuno- munomodulatory responses in target tissue [2, 15•]. suppressive capacity [27]. Several protocols for cell cul- Adipose-derived MSCs routinely are obtained enzymati- ture and expansion have been established, and many ef- cally and may undergo prolonged ex vivo expansion, with forts have been aimed at finding optimal conditions for significant senescence and a decline in multipotency. In addi- clinical-scale production of MSCs for cellular and gene tion, the technique is fraught with complex regulatory issues. therapy for inherited and acquired diseases [28]. This review presents an overview of the knowledge and Although many ex vivo and in vitro protocols have been clinical applications of adult MSCs, highlighting the role proposed, only a few studies have been done on the clinical Lipogems® technology has played in regenerative medicine applications of MSCs. The benefit of bone marrow MSC ther- so far. The urgent need to find new therapies for chronic im- apy in improving liver fibrosis was described in 11 patients munologic and degenerative diseases prompted many investi- with alcoholic cirrhosis [29]. Another study in two patients gators to search for products containing progenitor cells while with compensated cirrhosis investigated whether intraportal avoiding the problems and restrictions related to enzymatic injection of autologous bone marrow-derived MSCs com- manipulation and cell expansion in accordance with good bined with pioglitazone could stop or reduce liver fibrosis. manufacturing practice (GMP) rules [16, 17]. Although the results were encouraging, studies with more The availability of minimally manipulated products based patients are needed to prove the effectiveness of this clinical on adequate MSC content has resulted in shorter procedure application [30, 31]. times and the ability to apply autologous grafts in a one-step In 2010, Mazzini and Ferrero [32] began the first intervention. The Lipogems® technology guarantees both clinical trial to use bone marrow-derived MSCs to treat these requirements in an easy-to-use, rapid, and disposable amyotrophic lateral sclerosis and obtained promising re- adipose tissue transfer device and represents a very promising sults regarding the safety and usefulness of this proce- approach. dure. Moreover, a recent review on the treatment of spi- nal cord injuries with bone marrow MSC transplantation MSCs, the Medicine of the Future: Sources and Purposes in 20 patients reported convincing functional improve- ment [33]. More recently, multiple intramedullary and MSCs can proliferate in vitro and have multipotent differenti- intradural transplantations of MSCs were shown to ation properties. They also are strong immune modulators, achieve more satisfying results versus a single transplant inhibiting proinflammatory processes and stimulating anti- [34]. In 2005, a preliminary clinical trial using adipose- inflammatory mechanisms. These features may be exploited derivedMSCstotreatCrohn’s fistula was described, but to treat specific degenerative and inflammatory diseases in the further studies with larger patient samples are needed to near future; thus, research into the isolation, manipulation, and prove the feasibility of this application [35]. expansion of MSCs is increasing. All the aforementioned clinical trials were hampered by MSCs can be selected in culture from almost any tissue, complex and time-consuming enzymatic manipulation of including dental pulp, periodontal ligament, bone marrow, MSCs, as well as the extra centrifugation step(s) needed to fetal membranes, and placenta [18, 19]. Recently, obtain an adequate amount of cells. Because of the need to they were recognized in vivo as being derived from avoid these cumbersome procedures, the search for newer and perivascular cells [20, 21] and hence Binjury-specific^ better sources and processing strategies became increasingly cells. Indeed, MSCs detach from vessels
Load more

Recommended publications
  • CD34 Negative Hematopoietic Stem Cells
    Sysmex Journal International Vol.12 No.1 (2002) REVIEW ARTICLE CD34 Negative Hematopoietic Stem Cells Fu-sheng WANG R&D, Sysmex Corporation of America, Gilmer Road 6699 RFD, Long Grove, IL 60047-9596, USA. Key Words SERIES 14 CD34– HSC, Biology, Clinical Application Received 2 April, 2002; Accepted 12 April, 2002 INTRODUCTION quent studies3-10), have significantly challenged the exist- ing concepts in stem cell biology and related clinical Two of the most exciting breakthroughs in hematopoietic applications, such as stem cell transplantation and gene stem cell (HSC) research were first, the discovery of therapy4). Therefore, it is not surprising that many HSC CD34 expression on HSC, anti-CD34 antibody develop- investigators have used some interesting titles for their ment and its applications in HSC transplantation1, 2); and papers, and commonly question marks have appeared in secondly, the recent discovery of CD34 negative (CD34–) the article titles. HSC3-10). These discoveries, together with the success in For example: studies of other stem cells, have resulted in the emer- • CD34– stem cells as the earliest precursors of gence of novel clinical treatments in stem cell regenera- hematopoietic progeny5) tive medicine. • Hematopoietic stem cells: Are they CD34-positive or CD34-negative?6) Following the studies of CD34 by Civin1) in 1988, CD34 • CD34+ or CD34–: Does it really Matter? 7) antibody selected cells were successfully used for the • Who is hematopoietic stem cell: CD34+ or CD34–? 8) reconstruction of hematopoiesis in lethally
    [Show full text]
  • Chondrogenesis of Mesenchymal Stem Cells in a Novel Hyaluronate-Collagen-Tricalcium Phosphate Scaffolds for Knee Repair F.G
    EuropeanF Meng et Cells al. and Materials Vol. 31 2016 (pages 79-94) DOI: 10.22203/eCM.v031a06 TCP-COL-HA scaffolds for cartilage ISSN regeneration 1473-2262 CHONDROGENESIS OF MESENCHYMAL STEM CELLS IN A NOVEL HYALURONATE-COLLAGEN-TRICALCIUM PHOSPHATE SCAFFOLDS FOR KNEE REPAIR F.G. Meng§, Z.Q. Zhang§, G.X. Huang, W.S. Chen, Z.J. Zhang, A.S. He and W.M. Liao* Department of Joint Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China §These two authors contributed equally to this work. Abstract Introduction Scaffolds are expected to play a key role in the induction Damaged articular cartilage has poor self-repair capability of chondrogenesis of mesenchymal stem cells (MSCs) owing to the low metabolic rate of chondrocytes (Chen for cartilage tissue regeneration. Here, we report the et al., 2009; Hunziker, 2002; Steadman et al., 2002). development of a novel tricalcium phosphate-collagen- Tissue engineering is considered a potential strategy hyaluronate (TCP-COL-HA) scaffold that can function as for regenerating damaged tissue (Jackson and Simon, a stem cell carrier to induce chondrogenesis and promote 1999). Mesenchymal stem cells (MSCs) are an especially cartilage repair, and the investigation of chondroinductive promising tool since they can be easily isolated from bone properties of scaffolds containing varying amounts of TCP, marrow and expanded in vitro without the loss of their COL and HA. TCP-COL-HA scaffolds, as well as TCP- capacity to differentiate into various cell types, including COL scaffolds at two different TCP/COL ratios (50:50 and chondrocytes and osteoblasts (Caplan, 2005).
    [Show full text]
  • Applications of Mesenchymal Stem Cells in Skin Regeneration and Rejuvenation
    International Journal of Molecular Sciences Review Applications of Mesenchymal Stem Cells in Skin Regeneration and Rejuvenation Hantae Jo 1,† , Sofia Brito 1,†, Byeong Mun Kwak 2,3,† , Sangkyu Park 4,* , Mi-Gi Lee 5,* and Bum-Ho Bin 1,4,* 1 Department of Applied Biotechnology, Ajou University, Suwon 16499, Korea; [email protected] (H.J.); sofi[email protected] (S.B.) 2 Department of Meridian and Acupoint, College of Korean Medicine, Semyung University, Chungbuk 27136, Korea; [email protected] 3 School of Cosmetic Science and Beauty Biotechnology, Semyung University, 65 Semyung-ro, Jecheon-si, Chungcheongbuk-do 27136, Korea 4 Department of Biological Sciences, Ajou University, Suwon 16499, Korea 5 Bio-Center, Gyeonggido Business and Science Accelerator, Suwon 16229, Korea * Correspondence: [email protected] (S.P.); [email protected] (M.-G.L.); [email protected] (B.-H.B.); Tel.: +82-31-219-2967 (S.P.); +82-31-888-6952 (M.-G.L.); +82-031-219-2816 (B.-H.B.) † These authors contributed equally to this study. Abstract: Mesenchymal stem cells (MSCs) are multipotent stem cells derived from adult stem cells. Primary MSCs can be obtained from diverse sources, including bone marrow, adipose tissue, and umbilical cord blood. Recently, MSCs have been recognized as therapeutic agents for skin regeneration and rejuvenation. The skin can be damaged by wounds, caused by cutting or breaking of the tissue, and burns. Moreover, skin aging is a process that occurs naturally but can be worsened by environmental pollution, exposure to ultraviolet radiation, alcohol consumption, tobacco use, and undernourishment. MSCs have healing capacities that can be applied in damaged and aged Citation: Jo, H.; Brito, S.; Kwak, B.M.; Park, S.; Lee, M.-G.; Bin, B.-H.
    [Show full text]
  • Application Note
    Osteogenic Differentiation and Analysis of MSC Application Note Background Characterization and pancreatic islet cells, has also been observed in vitro when specific culture Mesenchymal stem cells (MSC) are According to the position paper pub- conditions and stimuli are applied [1]. fibroblastoid multipotent adult stem cells lished by the International Society for The directed differentiation of MSC is with a high capacity for self-renewal. So Cellular Therapy (ISCT), MSC express the carried out in vitro using appropriate far, these cells have been isolated from surface markers CD73, CD90 and CD105 differentiation media, such as the ready- several human tissues, including bone and stain negative for CD14 or CD11b, to-use PromoCell MSC Differentiation marrow, adipose tissue, umbilical cord CD34, CD45, CD79α or CD19, and HLA- Media (see below for differentiation matrix, tendon, lung, and the periosteum DR [3]. In addition to surface marker protocol). Terminally differentiated cells [1]. Recently it has been shown that MSC analysis, the most common and reliable are histochemically stained to determine originate from the perivascular niche, a way to identify a population of MSC is their respective identities (see below for tight network present throughout the to verify their multipotency. MSC can staining protocol). vasculature of the whole body. These differentiate into adipocytes, osteoblasts, perivascular cells lack endothelial and he- myocytes, and chondrocytes in vivo matopoietic markers, e.g. CD31, CD34 and in vitro [1,4]. Trans-differentiation
    [Show full text]
  • Characterization of Embryonic Stem Cell-Differentiated Cells As Mesenchymal Stem Cells
    The University of Southern Mississippi The Aquila Digital Community Honors Theses Honors College Fall 12-2015 Characterization of Embryonic Stem Cell-Differentiated Cells as Mesenchymal Stem Cells Rachael N. Kuehn University of Southern Mississippi Follow this and additional works at: https://aquila.usm.edu/honors_theses Part of the Cell Biology Commons Recommended Citation Kuehn, Rachael N., "Characterization of Embryonic Stem Cell-Differentiated Cells as Mesenchymal Stem Cells" (2015). Honors Theses. 349. https://aquila.usm.edu/honors_theses/349 This Honors College Thesis is brought to you for free and open access by the Honors College at The Aquila Digital Community. It has been accepted for inclusion in Honors Theses by an authorized administrator of The Aquila Digital Community. For more information, please contact [email protected]. The University of Southern Mississippi Characterization of Embryonic Stem Cell-Differentiated Cells as Mesenchymal Stem Cells by Rachael Nicole Kuehn A Thesis Submitted to the Honors College of The University of Southern Mississippi in Partial Fulfillment of the Requirements for the Degree of Bachelor of Science in the Department of Biological Sciences December 2015 ii Approved by ______________________________ Yanlin Guo, Ph.D., Thesis Adviser Professor of Biological Sciences ______________________________ Shiao Y. Wang, Ph.D., Chair Department of Biological Sciences ______________________________ Ellen Weinauer, Ph.D., Dean Honors College iii ABSTRACT Embryonic stem cells (ESCs), due to their ability to differentiate into different cell types while still maintaining a high proliferation capacity, have been considered as a potential cell source in regenerative medicine. However, current ESC differentiation methods are low yielding and create heterogeneous cell populations.
    [Show full text]
  • Characterization of Mesenchymal
    McCorry et al. Stem Cell Research & Therapy (2016) 7:39 DOI 10.1186/s13287-016-0301-8 RESEARCH Open Access Characterization of mesenchymal stem cells and fibrochondrocytes in three-dimensional co-culture: analysis of cell shape, matrix production, and mechanical performance Mary Clare McCorry1, Jennifer L. Puetzer1 and Lawrence J. Bonassar1,2* Abstract Background: Bone marrow mesenchymal stem cells (MSCs) have shown positive therapeutic effects for meniscus regeneration and repair. Preliminary in vitro work has indicated positive results for MSC applications for meniscus tissue engineering; however, more information is needed on how to direct MSC behavior. The objective of this study was to examine the effect of MSC co-culture with primary meniscal fibrochondrocytes (FCCs) in a three- dimensional collagen scaffold in fibrochondrogenic media. Co-culture of MSCs and FCCs was hypothesized to facilitate the transition of MSCs to a FCC cell phenotype as measured by matrix secretion and morphology. Methods: MSCs and FCCs were isolated from bovine bone marrow and meniscus, respectively. Cells were seeded in a 20 mg/mL high-density type I collagen gel at MSC:FCC ratios of 0:100, 25:75, 50:50, 75:25, and 100:0. Constructs were cultured for up to 2 weeks and then analyzed for cell morphology, glycosaminoglycan content, collagen content, and production of collagen type I, II, and X. Results: Cells were homogeneously mixed throughout the scaffold and cells had limited direct cell–cell contact. After 2 weeks in culture, MSCs transitioned from a spindle-like morphology toward a rounded phenotype, while FCCs remained rounded throughout culture. Although MSC shape changed with culture, the overall size was significantly larger than FCCs throughout culture.
    [Show full text]
  • ©Ferrata Storti Foundation
    Hematopoietic Stem Cells • Research Paper Mesenchymal stem cells are present in peripheral blood and can engraft after allogeneic hematopoietic stem cell transplantation [haematologica] 2004;89:1421-1427 EVA MARÍA VILLARON ABSTRACT JULIA ALMEIDA NATALIA LÓPEZ-HOLGADO Background and Objectives. Whether human mesenchymal stem cells (MSC) can be MIGUEL ALCOCEBA transplanted is controversial and their presence in peripheral blood is not fully accepted. LUIS IGNACIO SÁNCHEZ-ABARCA In the present study we have analyzed whether, within the allogeneic transplantation set- FERMIN MARTIN SANCHEZ-GUIJO ting, MSC are of host or donor origin. MERCEDES ALBERCA Design and Methods. Bone marrow MSC from 19 patients who had undergone allo- JOSE ANTONIO PÉREZ-SIMON, geneic transplantation were expanded and identified using immunophenotypic markers. JESUS FERNANDO SAN MIGUEL After that, chimerism studies were performed using reverse transcription polymerase MARÍA CONSUELO DEL CAÑIZO chain reaction of short tandem repeat (STR) loci. Analyses were carried out at different time-points after transplantation, with a total of 44 samples studied. Bone marrow was used as the source of stem cells for transplantation in 4 cases and peripheral blood in 15 cases. The conditioning regimen was standard in 9 patients and non-myeloablative in 10 patients. Results. Our results show that in the great majority of cases analyzed (17 out 19), MSC were of host origin. However, in 2 patients with multiple myeloma who had received a reduced intensity transplantation using peripheral blood stem cells, MSC were partially of donor origin (60.17% and 26.13% of total MSC). Interpretation and Conclusions. These findings indicate that after allogeneic trans- plantation MSC from the donor can engraft in bone marrow.
    [Show full text]
  • Mesenchymal Stem Cell Based Therapy for Parkinsonʼs Disease Neveen a Salem1,2*
    ISSN: 2469-570X Salem. Int J Stem Cell Res Ther 2019, 6:062 DOI: 10.23937/2469-570X/1410062 Volume 6 | Issue 1 International Journal of Open Access Stem Cell Research & Therapy REVIEW ARTICLE Mesenchymal Stem Cell Based Therapy for Parkinsonʼs Disease Neveen A Salem1,2* 1Department of Narcotics, Ergogenic Aids and Poisons, Medical Research Division, National Research Centre, Egypt Check for updates 2Department of Biochemistry, Faculty of Science, University of Jeddah, Saudi Arabia *Corresponding author: Neveen A Salem, Department of Narcotics, Ergogenic Aids and Poisons Department, Medical Research Division, National Research Centre, Giza, Egypt, Tel: 202(33335966), Fax: 202(33370931) Abstract Etiology and risk factors Parkinson’s disease (PD) is a chronic, progressive, neu- Parkinsonian symptoms can arise from either the rodegenerative disease with a multifactorial etiology, the neuropathologic condition of PD (idiopathic PD [iPD]) predominant pathology of PD is the loss of dopaminergic or other forms of parkinsonism. For neuropathologic cells in the substantia nigra. It is characterized by hall- mark signs of bradykinesia, rigidity, tremor, and postural PD, about 90% of cases are sporadic, with no clear instability. Medical and pharmacological treatments for etiology; an additional 10% have a genetic origin, and Parkinson’s disease are limited to the symptomatic relief at least 11 different linkages with 6 gene mutations of patients, and has failed to prevent or slow down the have been identified [5] Genetic forms of PD are seen process of neurodegeneration. Cell transplantation is a more frequently in young-onset PD. A combination of strategy with great potential for the treatment of Parkin- son’s disease, Mesenchymal stem cells are a great ther- environmental factors or toxins, genetic susceptibili- apeutic cell source because they are easy accessible.
    [Show full text]
  • Exploration of Alternative Splicing Events in Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells
    G C A T T A C G G C A T genes Article Exploration of Alternative Splicing Events in Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells Ji-Eun Jeong 1, Binna Seol 1, Han-Seop Kim 1, Jae-Yun Kim 1,2 and Yee-Sook Cho 1,2,* 1 Stem Cell Research Laboratory, Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea; [email protected] (J.-E.J.); [email protected] (B.S.); [email protected] (H.-S.K.); [email protected] (J.-Y.K.) 2 Department of Bioscience, KRIBB School, University of Science & Technology, 113 Gwahak-ro, Yuseong-gu, Daejeon 34113, Korea * Correspondence: [email protected]; Tel.: +82-42-860-4479; Fax: +82-42-860-4608 Abstract: Although comparative genome-wide transcriptomic analysis has provided insight into the biology of human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), the distinct alternative splicing (AS) signatures of iMSCs remain elusive. Here, we performed Illumina RNA sequencing analysis to characterize AS events in iMSCs compared with tissue-derived MSCs. A total of 4586 differentially expressed genes (|FC| > 2) were identified between iMSCs and umbilical cord blood-derived MSCs (UCB-MSCs), including 2169 upregulated and 2417 downregulated genes. Of these, 164 differentially spliced events (BF > 20) in 112 genes were identified between iMSCs and UCB-MSCs. The predominant type of AS found in iMSCs was skipped exons (43.3%), followed by retained introns (19.5%), alternative 30 (15.2%) and 50 (12.8%) splice sites, and mutually exclusive exons (9.1%).
    [Show full text]
  • Instant Stem Cell Therapy: Characterization and Concentration of Human Mesenchymal Stem Cells in Vitro
    PEuropean Kasten et Cells al. and Materials Vol. 16 2008 (pages 47-55) DOI: 10.22203/eCM.v016a06 In stant stemISSN cell 1473-2262 therapy INSTANT STEM CELL THERAPY: CHARACTERIZATION AND CONCENTRATION OF HUMAN MESENCHYMAL STEM CELLS IN VITRO P. Kasten1*, I. Beyen1, M. Egermann1, A.J. Suda1, A.A. Moghaddam2, G. Zimmermann2, R. Luginbühl3 1 Orthopaedic Surgery Hospital, University of Heidelberg, Schlierbacher Landstr. 200a, D-69118 Heidelberg, Germany 2 Trauma Center Ludwigshafen, Ludwigshafen, Germany, 3 Dr. hc Robert Mathys Foundation, Bettlach, Switzerland Abstract Introduction In regenerative medicine, there is an approach to avoid The use of mesenchymal stem cells (MSC) is the principal expansion of the mesenchymal stem cell (MSC) before part of the tissue engineering approach to regenerate tissue implantation. The aim of this study was to compare methods defects. MSC are contained in bone marrow (BM) for instant MSC therapy by use of a portable, automatic aspirates in a concentration of approximately 10-100 MSC and closed system centrifuge that allows for the per 1x106 BM cells (Bruder et al., 1994; Campagnoli et concentration of MSCs. The main outcome measures were al., 2001; Hernigou et al., 2005; Prockop et al., 2000; the amount of MSCs per millilitre of bone marrow (BM), Wexler et al., 2003). For clinical use, e.g. to accelerate clusters of differentiation (CD), proliferation and bone healing, high cell numbers are needed depending differentiation capacities of the MSC. A volume reduction on the size of the bone defect (Bruder et al., 1998; Quarto protocol was compared to the traditional laboratory methods et al., 2001).
    [Show full text]
  • On the Origin and Impact of Mesenchymal Stem Cell Heterogeneity: New Insights and Emerging Tools for Single Cell Analysis
    EuropeanCM McLeod Cells and and RL Materials Mauck Vol. 34 2017 (pages 217-231) DOI: 10.22203/eCM.v034a14 MSC heterogeneity and single ISSN cell 1473-2262 analysis ON THE ORIGIN AND IMPACT OF MESENCHYMAL STEM CELL HETEROGENEITY: NEW INSIGHTS AND EMERGING TOOLS FOR SINGLE CELL ANALYSIS C.M. McLeod1,2,3 and R.L. Mauck1,2,3* 1 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA 2 McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 3 Translational Musculoskeletal Research Center, Philadelphia VA Medical Center, Philadelphia, PA 19104, USA. Abstract Mesenchymal stem cells (MSCs) display substantial cell-to-cell variation. This heterogeneity manifests among donors, among tissue sources, and within cell populations. Such pervasive variability complicates the use of MSCs in regenerative applications and may limit their therapeutic efficacy. Most conventional assays measure MSC properties in bulk and, as a consequence, mask this cell-to-cell variation. Recent studies have identified extensive variability amongst and within clonal MSC populations, in dimensions including functional differentiation capacity, molecular state (e.g. epigenetic, transcriptomic, and proteomic status), and biophysical properties. While the origins of these variations remain to be elucidated, potential mechanisms include in vivo micro-anatomical heterogeneity, epigenetic bistability, and transcriptional fluctuations. Emerging tools
    [Show full text]
  • Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine
    biomolecules Review Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine Wee Kiat Ong 1,*, Smarajit Chakraborty 2 and Shigeki Sugii 2,3,* 1 School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Selangor, Malaysia 2 Institute of Bioengineering and Bioimaging (IBB), A*STAR, 31 Biopolis Way, Singapore 138669, Singapore; [email protected] 3 Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore * Correspondence: [email protected] (W.K.O.); [email protected] (S.S.) Abstract: Adipose-derived stem cells (ASCs) have been increasingly used as a versatile source of mesenchymal stem cells (MSCs) for diverse clinical investigations. However, their applications often become complicated due to heterogeneity arising from various factors. Cellular heterogeneity can occur due to: (i) nomenclature and criteria for definition; (ii) adipose tissue depots (e.g., subcutaneous fat, visceral fat) from which ASCs are isolated; (iii) donor and inter-subject variation (age, body mass index, gender, and disease state); (iv) species difference; and (v) study design (in vivo versus in vitro) and tools used (e.g., antibody isolation and culture conditions). There are also actual differences in resident cell types that exhibit ASC/MSC characteristics. Multilineage-differentiating stress-enduring (Muse) cells and dedifferentiated fat (DFAT) cells have been reported as an alternative or derivative source of ASCs for application in regenerative medicine. In this review, we discuss these factors that contribute to the heterogeneity of human ASCs in detail, and what should be taken into consideration Citation: Ong, W.K.; Chakraborty, S.; for overcoming challenges associated with such heterogeneity in the clinical use of ASCs.
    [Show full text]