Skip to main content
SpringerLink
Log in

Mesenchymal Stem Cells: The Past Present and Future

  • Chapter
  • First Online:
Cell Biology and Translational Medicine, Volume 11

Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1312))

Abstract

The biomedical applications of mesenchymal stem cells (MSCs) have gained expanding attention over the past three decades. MSCs are easily obtained from various tissue types (e.g. bone marrow, fat, cord blood, etc.), are capable of self-renewal, and could be induced to differentiate into several cell lineages for countless biomedical applications. In addition, when transplanted, MSCs are not detected by immune surveillance, thus do not lead to graft rejection. Moreover, they can home towards affected tissues and induce their therapeutic effect in a cell-base and/or a cell-free manner. These properties, and many others, have made MSCs appealing therapeutic cell candidates (for cell and/or gene therapy) in myriad clinical conditions. However, similar to any other therapeutic tool, MSCs still have their own limitations and grey areas that entail more research for better understanding and optimization. Herein, we present a brief overview of various pre-clinical/clinical applications of MSCs in regenerative medicine and discuss limitations and future challenges.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AAV:

Adeno-Associated Virus

AD-MSCs:

Adipose tissue derived Mesenchymal Stem Cells

ALS:

Amyotrophic Lateral Sclerosis

BAX:

Bcl-2-associated X protein

BDNF:

Brain-derived neurotropic factor

BM:

Bone Marrow

BM-MSCs:

Marrow-derived Mesenchymal Stem Cells

BMP:

Bone morphogenetic protein

Caspases:

Cysteine-aspartic proteases

CDs:

Cluster of Differentiations

CFU-Fs:

Colony Forming Unit-Fibroblasts

CM:

Condition Media

CXCR2:

Chemokine (c-x-c motif) Receptor 2

DCM:

Dilated Cardiomyopathy

ECM:

Extracellular Matrix

EVs:

Extracellular Vesicles

GFs:

Growth Factors

GvHD:

Graft versus Host Disease

HGF:

Hepatocyte growth factor

hHF-MSCs:

human hair follicle Mesenchymal Stem Cells

hPMSCs:

Human placental Mesenchymal Stem Cells

IGF:

Insulin-like Growth Factor

ILK:

Integrin-Linked Kinase

ILs:

Interleukins

ISCT:

International Society for Cellular Therapy

miRNA:

MicroRNA

mMSCs:

mouse Mesenchymal Stem Cells

MSCs:

Mesenchymal Stem Cells

MVs:

Microvesicles

NGF:

Nerve Growth Factor

NPs:

Nanoparticles

PAI-1:

Plasminogen activator inhibitor 1

PLGA:

Poly (Lactic-co-Glycolic Acid)

PMA:

Phorbol 12-myristate 13-acetate

rhBMP:

Recombinant human Bone Morphogenetic Protein

RNAi:

RNA interference

ROS:

Reactive Oxygen Species

SCF:

Stem Cell Factor

TGF-β1:

Transforming Growth Factor-β1

TNTs:

Tunneling nanotubes

tTG:

tissue Transglutaminase

UCB-MSCs:

Umbilical Cord Blood Mesenchymal Stem Cells

VEGF:

Vascular Endothelial Growth Factor

WJSCs:

Wharton’s Jelly Stem Cells

References

  • Abdel Aal S, Abdelrahman S, Raafat N (2019) Comparative therapeutic effects of mesenchymal stem cells versus their conditioned media in alleviation of CCL4-induced liver fibrosis in rats: Histological and biochemical study. J Med Histol 3(1):1–20

    Article  Google Scholar 

  • Afanasyev BV, Elstner E, Zander AR (2009) AJ Friedenstein, founder of the mesenchymal stem cell concept. Cell Ther Transplant 1(3):35–38

    Google Scholar 

  • AHN SY (2020) The role of MSCs in the tumor microenvironment and tumor progression. Anticancer Res 40(6):3039–3047

    Article  CAS  Google Scholar 

  • Anversa P, Kajstura J, Leri A (2004) Circulating progenitor cells: search for an identity. Am Heart Assoc 3158–3160

    Google Scholar 

  • Attia N et al (2014) Behaviour and ultrastructure of human bone marrow-derived mesenchymal stem cells immobilised in alginate-poly-l-lysine-alginate microcapsules. Journal of microencapsulation 31(6):579–589

    Google Scholar 

  • Attia N et al (2018) Stem cell-based gene delivery mediated by cationic niosomes for bone regeneration. Nanomedicine: Nanotechnology, Biology and Medicine 14(2):521–531

    Google Scholar 

  • Babenko VA et al (2018) Miro1 enhances mitochondria transfer from multipotent mesenchymal stem cells (MMSC) to neural cells and improves the efficacy of cell recovery. Molecules 23(3):687

    Google Scholar 

  • Bagno L et al (2018) Mesenchymal stem cell-based therapy for cardiovascular disease: progress and challenges. Mol Ther 26(7):1610–1623

    Article  CAS  Google Scholar 

  • Berebichez-Fridman R, Montero-Olvera PR (2018) Sources and clinical applications of mesenchymal stem cells: state-of-the-art review. Sultan Qaboos Univ Med J 18(3):e264

    Article  Google Scholar 

  • Berndt B, Zanker KS, Dittmar T (2013) Cell fusion is a potent inducer of aneuploidy and drug resistance in tumor cell/ normal cell hybrids. Crit Rev Oncog 18(1–2):97–113

    Article  Google Scholar 

  • Bian S et al (2014) Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model. Journal of molecular medicine 92(4):387–397

    Google Scholar 

  • Boukelmoune N et al (2018) Mitochondrial transfer from mesenchymal stem cells to neural stem cells protects against the neurotoxic effects of cisplatin. Acta neuropathologica communications 6(1):1–13

    Google Scholar 

  • Butler J et al (2017) Intravenous allogeneic mesenchymal stem cells for nonischemic cardiomyopathy: safety and efficacy results of a phase II-A randomized trial. Circulation Research 120(2):332–340

    Google Scholar 

  • Candini O et al (2015) Mesenchymal progenitors aging highlights a mi R-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis. Stem Cells 33(3):939–950

    Google Scholar 

  • Cao H et al (2011) Characterization of immortalized mesenchymal stem cells derived from foetal porcine pancreas. Cell proliferation 44(1):19–32

    Google Scholar 

  • Cao B et al (2014) Stem cells loaded with nanoparticles as a drug carrier for in vivo breast cancer therapy. Advanced Materials 26(27):4627–4631

    Google Scholar 

  • Caplan AI (2019a) There is no “stem cell mess”. Tissue Eng Part B Rev 25(4):291–293

    Article  Google Scholar 

  • Caplan AI (2019b) Medicinal signalling cells: they work, so use them. Nature 566(7742):39–40

    Article  CAS  Google Scholar 

  • Carlini FR et al (2019) Transcriptome analysis of mesenchymal stem cells from multiple myeloma patients reveals downregulation of genes involved in cell cycle progression, immune response, and bone metabolism. Sci Rep 9(1)

    Google Scholar 

  • Chen J-J, Zhou S-H (2011) Mesenchymal stem cells overexpressing MiR-126 enhance ischemic angiogenesis via the AKT/ERK-related pathway. Cardiology journal 18(6):675–681

    Google Scholar 

  • Chen FH et al (2007) Mesenchymal stem cells. In: Principles of tissue engineering. Elsevier, pp 823–843

    Google Scholar 

  • Chen J et al (2011) Simultaneous regeneration of articular cartilage and subchondral bone in vivo using MSCs induced by a spatially controlled gene delivery system in bilayered integrated scaffolds. Biomaterials 32(21):4793–4805

    Google Scholar 

  • Chen B et al (2016) Protective effect of Ad-VEGF-Bone mesenchymal stem cells on cerebral infarction. Turkish neurosurgery 26(1):8

    Google Scholar 

  • Cheung WY et al (2018) Efficient nonviral transfection of human bone marrow mesenchymal stromal cells shown using placental growth factor overexpression. Stem Cells International 2018

    Google Scholar 

  • Chu Y et al (2014) Human placenta mesenchymal stem cells expressing exogenous kringle1-5 protein by fiber-modified adenovirus suppress angiogenesis. Cancer Gene Therapy 21(5):200–208

    Google Scholar 

  • Chudickova M et al (2019) The effect of Wharton jelly-derived mesenchymal stromal cells and their conditioned media in the treatment of a rat spinal cord injury. International journal of molecular sciences 20(18):4516

    Google Scholar 

  • Cianfarani F et al (2013) Diabetes impairs adipose tissue–derived stem cell function and efficiency in promoting wound healing. Wound repair and regeneration 21(4):545–553

    Google Scholar 

  • Copland IB, Galipeau J (2011) Death and inflammation following somatic cell transplantation. In: Seminars in immunopathology. Springer

    Google Scholar 

  • Court AC et al (2020) Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response. EMBO reports 21(2):e48052

    Google Scholar 

  • Curtin CM et al (2012) Innovative collagen nano-hydroxyapatite scaffolds offer a highly efficient non-viral gene delivery platform for stem cell-mediated bone formation. Advanced materials 24(6):749–754

    Google Scholar 

  • Dahbour S et al (2017) Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: clinical, ophthalmological and radiological assessments of safety and efficacy. CNS neuroscience & therapeutics 23(11):866–874

    Google Scholar 

  • Dai T et al (2013) Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system. International journal of pharmaceutics 456(1):186–194

    Google Scholar 

  • Detante O et al (2012) Magnetic resonance imaging and fluorescence labeling of clinical-grade mesenchymal stem cells without impacting their phenotype: study in a rat model of stroke. Stem cells translational medicine 1(4):333–340

    Google Scholar 

  • Dominici MJC (2006) Minimum criteria for defining multipotent stem cells-The ISCT position statement. Cytotherapy 8(4):315–317

    Google Scholar 

  • Dong H-J et al (2019) Meeting prometheus: the mechanism of MSC-based therapies; cell replacement or “Pretended Bystander Effects”? Turkish neurosurgery 29(4)

    Google Scholar 

  • Elgaz S et al (2019) Clinical use of mesenchymal stromal cells in the treatment of acute graft-versus-host disease. Transfus Med Hemother 46(1):27–34

    Article  Google Scholar 

  • Fernandes-Cunha GM et al (2019) Corneal wound healing effects of mesenchymal stem cell secretome delivered within a viscoelastic gel carrier. Stem cells translational medicine 8(5):478–489

    Google Scholar 

  • Ferrero I et al (2008) Bone marrow mesenchymal stem cells from healthy donors and sporadic amyotrophic lateral sclerosis patients. Cell transplantation 17(3):255–266

    Google Scholar 

  • Figeac F et al (2014) Nanotubular crosstalk with distressed cardiomyocytes stimulates the paracrine repair function of mesenchymal stem cells. Stem Cells 32(1):216–230

    Google Scholar 

  • Florea V et al (2017) Dose comparison study of allogeneic mesenchymal stem cells in patients with ischemic cardiomyopathy (the TRIDENT study). Circulation research 121(11):1279–1290

    Google Scholar 

  • Galland S, Stamenkovic IJT (2020) Mesenchymal stromal cells in cancer: a review of their immunomodulatory functions and dual effects on tumor progression. J Pathol 250(5):555–572

    Article  Google Scholar 

  • Geffner L et al (2008) Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell transplantation 17(12):1277–1293

    Google Scholar 

  • Ghavamzadeh A et al (2010) Co-transplantation of HLA-matched related donors culture-expanded mesenchymal stromal cells and hematopoietic stem cells in thalassemia major patients. Biology of Blood and Marrow Transplantation 16(2):S214

    Google Scholar 

  • Ghosh P, Goldschlager T, Itescu S (2013) Back pain—a clinical challenge addressed by Mesoblast using their mesenchymal precursor cells. Nature Outlook

    Google Scholar 

  • Gimbel M et al (2007) Repair of alveolar cleft defects: reduced morbidity with bone marrow stem cells in a resorbable matrix. Journal of Craniofacial Surgery 18(4):895–901

    Google Scholar 

  • Gimble JM et al (2008) In vitro differentiation potential of mesenchymal stem cells. Transfusion Medicine and Hemotherapy 35(3):228–238

    Google Scholar 

  • Gonzalez-Fernandez T et al (2016) Gene delivery of TGF-β3 and BMP2 in an MSC-laden alginate hydrogel for articular cartilage and endochondral bone tissue engineering. Tissue Engineering Part A 22(9–10):776–787

    Google Scholar 

  • Gonzalez-Fernandez T et al (2017) Mesenchymal stem cell fate following non-viral gene transfection strongly depends on the choice of delivery vector. Acta biomaterialia 55:226–238

    Google Scholar 

  • Haga H et al (2017) Extracellular vesicles from bone marrow-derived mesenchymal stem cells improve survival from lethal hepatic failure in mice. Stem cells translational medicine 6(4):1262–1272

    Google Scholar 

  • Hashemi M, Kalalinia F (2015) Application of encapsulation technology in stem cell therapy. Life Sci 143:139–146

    Article  CAS  Google Scholar 

  • He X et al (2014) Enhanced healing of rat calvarial defects with MSCs loaded on BMP-2 releasing chitosan/alginate/hydroxyapatite scaffolds. PLoS One 9(8):e104061

    Article  Google Scholar 

  • Heldman AW et al (2014) Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. Jama 311(1):62–73

    Google Scholar 

  • Hibi H et al (2006) Alveolar cleft osteoplasty using tissue-engineered osteogenic material. International journal of oral and maxillofacial surgery 35(6):551–555

    Google Scholar 

  • Hombach AA et al (2020) IL7-IL12 Engineered mesenchymal stem cells (MSCs) improve a CAR T cell attack against colorectal cancer cells. Cells 9(4):873

    Google Scholar 

  • Horwitz E et al (2005) Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 7(5):393–395

    Google Scholar 

  • Hu L et al (2016) Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Scientific reports 6:32993

    Google Scholar 

  • Hu C et al (2018) Regulation of the mitochondrial reactive oxygen species: strategies to control mesenchymal stem cell fates ex vivo and in vivo. Journal of cellular and molecular medicine 22(11):5196–5207

    Google Scholar 

  • Ionescu L et al (2012) Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action. Journal of Physiology-Lung Cellular and Molecular Physiology 303(11):L967–L977

    Google Scholar 

  • Iseri K et al (2016) Therapeutic effects and mechanism of conditioned media from human mesenchymal stem cells on anti-GBM glomerulonephritis in WKY rats. American Journal of Physiology-Renal Physiology 310:F1182–F1191

    Google Scholar 

  • Islam MN et al (2012) Mitochondrial transfer from bone-marrow–derived stromal cells to pulmonary alveoli protects against acute lung injury. Nature medicine 18(5):759–765

    Google Scholar 

  • Jeon SY et al (2012) Co-delivery of SOX9 genes and anti-Cbfa-1 siRNA coated onto PLGA nanoparticles for chondrogenesis of human MSCs. Biomaterials 33(17):4413–4423

    Article  CAS  Google Scholar 

  • Jeong SR et al (2012) Hepatocyte growth factor reduces astrocytic scar formation and promotes axonal growth beyond glial scars after spinal cord injury. Experimental neurology 233(1):312–322

    Google Scholar 

  • Jiang D et al (2016) Mitochondrial transfer of mesenchymal stem cells effectively protects corneal epithelial cells from mitochondrial damage. Cell death & disease 7(11):e2467–e2467

    Google Scholar 

  • Katagiri W et al (2016) First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells. Head & face medicine 12(1):5

    Google Scholar 

  • Keilhoff G et al (2006) Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells. European Journal of Cell Biology 85(1):11–24

    Google Scholar 

  • Khatab S, et al (2020) MSC encapsulation in alginate microcapsules prolongs survival after intra-articular injection, a longitudinal in vivo cell and bead integrity tracking study. Cell Biology and Toxicology

    Google Scholar 

  • Kidd S et al (2010) Mesenchymal stromal cells alone or expressing interferon-β suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment. Cytotherapy 12(5):615–625

    Google Scholar 

  • Kim SM et al (2008) Gene therapy using TRAIL-secreting human umbilical cord blood–derived mesenchymal stem cells against intracranial glioma. Cancer research 68(23):9614–9623

    Google Scholar 

  • Kim SH et al (2011) Hypoxia-inducible vascular endothelial growth factor-engineered mesenchymal stem cells prevent myocardial ischemic injury. Molecular Therapy 19(4):741–750

    Google Scholar 

  • Laso-García F et al (2018) Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis. PLoS One 13(9):e0202590

    Google Scholar 

  • Lee S et al (2015) Cell adhesion and long-term survival of transplanted mesenchymal stem cells: a prerequisite for cell therapy. Oxidative medicine and cellular longevity 2015

    Google Scholar 

  • Li G et al (2009) Comparative proteomic analysis of mesenchymal stem cells derived from human bone marrow, umbilical cord, and placenta: implication in the migration. Proteomics 9(1):20–30

    Google Scholar 

  • Li L et al (2011) Silica nanorattle–doxorubicin-anchored mesenchymal stem cells for tumor-tropic therapy. ACS nano 5(9):7462–7470

    Google Scholar 

  • Li D et al (2013) Mesenchymal stem cells protect podocytes from apoptosis induced by high glucose via secretion of epithelial growth factor. Stem cell research & therapy 4(5):1–11

    Google Scholar 

  • Lim JY et al (2010) Microporation is a valuable transfection method for efficient gene delivery into human umbilical cord blood-derived mesenchymal stem cells. BMC biotechnology 10(1):–38

    Google Scholar 

  • Liu K et al (2014) Mesenchymal stem cells rescue injured endothelial cells in an in vitro ischemia–reperfusion model via tunneling nanotube like structure-mediated mitochondrial transfer. Microvascular research 92:10–18

    Google Scholar 

  • Lu S-S et al (2013) In vivo MR imaging of intraarterially delivered magnetically labeled mesenchymal stem cells in a canine stroke model. PloS one 8(2):e54963

    Google Scholar 

  • Ma Z et al (2013) Mesenchymal stem cell-cardiomyocyte interactions under defined contact modes on laser-patterned biochips. PLoS One 8(2):e56554

    Google Scholar 

  • Madeira C et al (2010) Nonviral gene delivery to mesenchymal stem cells using cationic liposomes for gene and cell therapy. BioMed Research International, 2010

    Google Scholar 

  • Mahrouf-Yorgov M et al (2017) Mesenchymal stem cells sense mitochondria released from damaged cells as danger signals to activate their rescue properties. Cell Death & Differentiation 24(7):1224–1238

    Google Scholar 

  • Malik YS et al (2018) Polylysine-modified polyethylenimine polymer can generate genetically engineered mesenchymal stem cells for combinational suicidal gene therapy in glioblastoma. Acta biomaterialia 80:144–153

    Google Scholar 

  • Mammana S et al (2019) Human gingival mesenchymal stem cells pretreated with vesicular moringin nanostructures as a new therapeutic approach in a mouse model of spinal cord injury. J Tissue Eng Regen Med 13(7):1109–1121

    Article  CAS  Google Scholar 

  • Mashal M et al (2017) Retinal gene delivery enhancement by lycopene incorporation into cationic niosomes based on DOTMA and polysorbate 60. Journal of controlled release 254:55–64

    Google Scholar 

  • Mashal M et al (2019) Gene delivery to the rat retina by non-viral vectors based on chloroquine-containing cationic niosomes. Journal of the controlled release 304:181–190

    Google Scholar 

  • Mehanna RA, et al (2015) The effect of bone marrow-derived mesenchymal stem cells and their conditioned media topically delivered in fibrin glue on chronic wound healing in rats. BioMed research international

    Google Scholar 

  • Mellott AJ, Forrest ML, Detamore MS (2013) Physical non-viral gene delivery methods for tissue engineering. Ann Biomed Eng 41(3):446–468

    Article  Google Scholar 

  • Mizrahi O et al (2013) BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells. Gene therapy 20(4):370–377

    Google Scholar 

  • Moku G et al (2019) Improving payload capacity and anti-tumor efficacy of mesenchymal stem cells using TAT peptide functionalized polymeric nanoparticles. Cancers (Basel):11(4)

    Google Scholar 

  • Moon H-H et al (2014) MSC-based VEGF gene therapy in rat myocardial infarction model using facial amphipathic bile acid-conjugated polyethyleneimine. Biomaterials 35(5):1744–1754

    Google Scholar 

  • Morbach S et al (2004) Regional differences in risk factors and clinical presentation of diabetic foot lesions. Diabetic Medicine 21(1):91–95

    Google Scholar 

  • Mueller SM, Glowacki J (2001) Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges. J Cell Biochem 82(4):583–590

    Article  CAS  Google Scholar 

  • Muhammad T et al (2019) Mesenchymal stem cell-mediated delivery of therapeutic adenoviral vectors to prostate cancer. Stem cell research & therapy 10(1):190

    Google Scholar 

  • Murray LM, Krasnodembskaya AD (2019) Concise review: intercellular communication via organelle transfer in the biology and therapeutic applications of stem cells. Stem Cells 37(1):14–25

    Article  Google Scholar 

  • Musiał-Wysocka A, Kot M, Majka M (2019) The pros and cons of mesenchymal stem cell-based therapies. Cell Transplant 28(7):801–812

    Article  Google Scholar 

  • Musial-Wysocka A, Kot M, Majka M (2019) The pros and cons of mesenchymal stem cell-based therapies. Cell Transplant 28(7):801–812

    Article  Google Scholar 

  • Muslimov AR et al (2020) Biomimetic drug delivery platforms based on mesenchymal stem cells impregnated with light-responsive submicron sized carriers. Biomaterials science 8(4):1137–1147

    Google Scholar 

  • Nakae M et al (2006) Effects of basic fibroblast growth factor on experimental diabetic neuropathy in rats. 55(5):1470–1477

    Google Scholar 

  • Nakajima M et al (2017) Mesenchymal stem cells overexpressing interleukin-10 promote neuroprotection in experimental acute ischemic stroke. Molecular Therapy-Methods & Clinical Development 6:102–111

    Google Scholar 

  • Nakashima S et al (2005) Highly efficient transfection of human marrow stromal cells by nucleofection. In: Transplant Proc. Elsevier

    Google Scholar 

  • Naoto K et al (2019) Mitochondria transfer from mesenchymal stem cells structurally and functionally repairs renal proximal tubular epithelial cells in diabetic nephropathy in vivo. Scientific Reports (Nature Publisher Group) 9(1)

    Google Scholar 

  • Neri S (2019) Genetic stability of mesenchymal stromal cells for regenerative medicine applications: a fundamental biosafety aspect. Int J Mol Sci 20(10)

    Google Scholar 

  • Niess H et al (2015) Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial. BMC cancer 15(1):237

    Google Scholar 

  • Nishiyama N et al (2005) Smart polymeric micelles for gene and drug delivery. Drug Discovery Today: Technologies 2(1):21–26

    Google Scholar 

  • Nissan X et al (2012) Unique preservation of neural cells in Hutchinson-Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA. Cell Reports 2(1):1–9

    Google Scholar 

  • Noiseux N et al (2006) Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Molecular Therapy 14(6):840–850

    Google Scholar 

  • Orozco L et al (2011) Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation 92(7):822–828

    Google Scholar 

  • Orozco L et al (2013) Treatment of knee osteoarthritis with autologous mesenchymal stem cells: a pilot study. Transplantation 95(12):1535–1541

    Google Scholar 

  • Orozco L et al (2014) Treatment of knee osteoarthritis with autologous mesenchymal stem cells: two-year follow-up results. Transplantation 97(11):e66–e68

    Google Scholar 

  • Otero L et al (2011) Late transplantation of allogeneic bone marrow stromal cells improves neurologic deficits subsequent to intracerebral hemorrhage. Cytotherapy 13(5):562–571

    Google Scholar 

  • Park HH, et al (2020) TGF-β secreted by human umbilical cord blood-derived mesenchymal stem cells ameliorates atopic dermatitis by inhibiting secretion of TNF-α and IgE STEM CELLS

    Google Scholar 

  • Pascucci L et al (2014) Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. Journal of Controlled Release 192:262–270

    Google Scholar 

  • Pires AO et al (2016) Unveiling the differences of secretome of human bone marrow mesenchymal stem cells, adipose tissue-derived stem cells, and human umbilical cord perivascular cells: a proteomic analysis. Stem cells and development 25(14):1073–1083

    Google Scholar 

  • Piri Z et al (2012) Interleukin-25 as a candidate gene in immunogene therapy of pancreatic cancer. Journal of Medical Hypotheses and Ideas 6(2):75–79

    Google Scholar 

  • Premer C et al (2019) Mesenchymal stem cell secretion of SDF-1α modulates endothelial function in dilated cardiomyopathy. Frontiers in Physiology 10:1182

    Google Scholar 

  • Qi S, Wu D (2013) Bone marrow-derived mesenchymal stem cells protect against cisplatin-induced acute kidney injury in rats by inhibiting cell apoptosis. Int J Mol Med 32(6):1262–1272

    Article  CAS  Google Scholar 

  • Raisin S et al (2017) Tripartite polyionic complex (PIC) micelles as non-viral vectors for mesenchymal stem cell siRNA transfection. Biomaterials science 5(9):1910–1921

    Google Scholar 

  • Rejman J et al (2010) mRNA transfection of cervical carcinoma and mesenchymal stem cells mediated by cationic carriers. J Control Release 147(3):385–391

    Article  CAS  Google Scholar 

  • Roch AM et al (2020) Therapeutic use of adipose-derived stromal cells in a murine model of acute pancreatitis Journal of Gastrointestinal Surgery 24(1):67–75

    Google Scholar 

  • Rodini CO et al (2018) Mesenchymal stem cells enhance tumorigenic properties of human glioblastoma through independent cell-cell communication mechanisms. Oncotarget 9(37):24766–24777

    Article  Google Scholar 

  • Rohart F et al (2016) A molecular classification of human mesenchymal stromal cells. Peer J 4:e1845

    Google Scholar 

  • Rong X et al (2019) Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway. Stem cell research & therapy 10(1):1–11

    Google Scholar 

  • Rossignoli F et al (2019) Inducible Caspase9-mediated suicide gene for MSC-based cancer gene therapy. cancer gene therapy 26(1):11–16

    Google Scholar 

  • Rostom DM et al (2020) The therapeutic potential of extracellular vesicles versus mesenchymal stem cells in liver damage, Tissue Engineering and Regenerative Medicine vol 17, pp 537–552

    Google Scholar 

  • Roura S, Bayes-Genis AJP (2019) Toward standardization of mesenchymal stromal cell-derived extracellular vesicles for therapeutic use: a call for action. Proteomics 19(1–2):1800397

    Google Scholar 

  • Ruppert KA et al (2018) Human mesenchymal stromal cell-derived extracellular vesicles modify microglial response and improve clinical outcomes in experimental spinal cord injury. Scientific reports 8(1):1–12

    Google Scholar 

  • Rustad KC, Gurtner GC (2012) Mesenchymal stem cells home to sites of injury and inflammation. Adv Wound Care 1(4):147–152

    Article  Google Scholar 

  • Ryu CH et al (2012) Valproic acid enhances anti-tumor effect of mesenchymal stem cell mediated HSV-TK gene therapy in intracranial glioma. Biochemical and biophysical research communications 421(3):585–590

    Google Scholar 

  • Sagaradze G et al (2019) Conditioned medium from human mesenchymal stromal cells: towards the clinical translation. International journal of molecular sciences 20(7):1656

    Google Scholar 

  • Sanchez MBH et al (2014) Human liver stem cells and derived extracellular vesicles improve recovery in a murine model of acute kidney injury. Stem cell research & therapy 5(6):124

    Google Scholar 

  • Sato H et al (2005) Epidermal growth factor receptor-transfected bone marrow stromal cells exhibit enhanced migratory response and therapeutic potential against murine brain tumors. Cancer gene therapy 12(9):757–768

    Google Scholar 

  • Seleci DA et al (2017) Tumor homing and penetrating peptide-conjugated niosomes as multi-drug carriers for tumor-targeted drug delivery. RSC advances 7(53):33378–33384

    Google Scholar 

  • Seo S et al (2011) The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity. Gene therapy 18(5):488–495

    Google Scholar 

  • Shahror RA et al (2020) Transplantation of mesenchymal stem cells overexpressing fibroblast growth factor 21 facilitates cognitive recovery and enhances neurogenesis in a mouse model of traumatic brain injury. Journal of Neurotrauma 37(1):14–26

    Google Scholar 

  • Shan X et al (2018) Adipose stem cells with conditioned media for treatment of acne vulgaris scar. Tissue Engineering and Regenerative Medicine 15(1):49–61

    Google Scholar 

  • Sheyn D et al (2010) Genetically modified mesenchymal stem cells induce mechanically stable posterior spine fusion. Tissue Engineering Part A 16(12):3679–3686

    Google Scholar 

  • Shibata T et al (2008) Transplantation of bone marrow–derived mesenchymal stem cells improves diabetic polyneuropathy in rats. Diabetes 57(11):3099–3107

    Google Scholar 

  • Shyu W-C et al (2007) Efficient tracking of non-iron-labeled mesenchymal stem cells with serial MRI in chronic stroke rats. Stroke 38(2):367–374

    Google Scholar 

  • Sinclair KA et al (2016) Characterization of intercellular communication and mitochondrial donation by mesenchymal stromal cells derived from the human lung. Stem cell research & therapy 7(1):91

    Google Scholar 

  • Son S et al (2015) Magnetofection mediated transient NANOG overexpression enhances proliferation and myogenic differentiation of human hair follicle derived mesenchymal stem cells. Bioconjugate chemistry 26(7):1314–1327

    Google Scholar 

  • Sottile F et al (2016) Mesenchymal stem cells generate distinct functional hybrids in vitro via cell fusion or entosis. Scientific reports 6:36863

    Google Scholar 

  • Srifa W et al (2020) Cas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice. Nature communications 11(1):1–14

    Google Scholar 

  • Sun Y, et al (2015) Mesenchymal stem cells from patients with rheumatoid arthritis display impaired function in inhibiting Th17 cells. Journal of immunology research

    Google Scholar 

  • Sylakowski K, Bradshaw A, Wells A (2020) Mesenchymal stem cell/multipotent stromal cell augmentation of wound healing: lessons from the physiology of matrix and hypoxia support. Am J Pathol

    Google Scholar 

  • Tao S-C et al (2017) Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics 7(1):180

    Google Scholar 

  • Tompkins BA et al (2018) Comparison of mesenchymal stem cell efficacy in ischemic versus nonischemic dilated cardiomyopathy. Journal of the American Heart Association 7(14):e008460

    Google Scholar 

  • Trachtenberg B, et al (2011) Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy. American heart journal 161(3): 487–493

    Google Scholar 

  • Tripodo G et al (2015) Mesenchymal stromal cells loading curcumin-INVITE-micelles: a drug delivery system for neurodegenerative diseases. Colloids and Surfaces B: Biointerfaces 125:300–308

    Google Scholar 

  • Trudel S et al (2001) Adenovector engineered interleukin-2 expressing autologous plasma cell vaccination after high-dose chemotherapy for multiple myeloma-a phase 1 study. Leukemia 15(5):846–854

    Google Scholar 

  • Tsai M-J et al (2014) Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats. Journal of biomedical science 21(1):1–12

    Google Scholar 

  • Vallabhaneni KC et al (2012) Vascular smooth muscle cells initiate proliferation of mesenchymal stem cells by mitochondrial transfer via tunneling nanotubes. Stem cells and development 21(17):3104–3113

    Google Scholar 

  • van Balkom, Bas WM et al (2019) Proteomic signature of Mesenchymal stromal cell-derived small extracellular vesicles. Proteomics 19(1–2):1800163

    Google Scholar 

  • Vaquero J, Zurita M (2011) Functional recovery after severe CNS trauma: current perspectives for cell therapy with bone marrow stromal cells. Progress Neurobiol 93(3):341–349

    Article  Google Scholar 

  • Vega A et al (2015) Treatment of knee osteoarthritis with allogeneic bone marrow mesenchymal stem cells: a randomized controlled trial. Transplantation 99(8):1681–1690

    Google Scholar 

  • Vizoso FJ et al (2017) Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine. International journal of molecular sciences 18(9):1852

    Google Scholar 

  • Vonk LA et al (2018) Mesenchymal stromal/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro. Theranostics 8(4):906

    Google Scholar 

  • Wagner W, Ho AD (2007) Mesenchymal stem cell preparations—comparing apples and oranges. Stem Cell Rev 3(4):239–248

    Article  Google Scholar 

  • Wagner W, Frobel J, Goetzke R (2016) Epigenetic quality check–how good are your mesenchymal stromal cells? Future Med 889–894

    Google Scholar 

  • Wang L et al (2000) Bone marrow stromal cells of bcl-2 transgenic mice express widespread Bcl-2 protein and reduce apoptosis in a serum-free medium. Am Heart Assoc 380–380

    Google Scholar 

  • Wang L et al (2016) Extracellular vesicles released from human umbilical cord-derived mesenchymal stromal cells prevent life-threatening acute graft-versus-host disease in a mouse model of allogeneic hematopoietic stem cell transplantation. Stem cells and development 25(24):1874–1883

    Google Scholar 

  • Wang H et al (2019a) PTPN21 overexpression promotes osteogenic and adipogenic differentiation of bone marrow-derived mesenchymal stem cells but inhibits the immunosuppressive function. 2019

    Google Scholar 

  • Wang X et al (2019b) Efficient lung cancer-targeted drug delivery via a nanoparticle/MSC system. Acta Pharmaceutica Sinica 9(1):167–176

    Google Scholar 

  • Wang J et al (2020) MiR-101a loaded extracellular nanovesicles as bioactive carriers for cardiac repair. Nanomedicine 27:102201

    Article  CAS  Google Scholar 

  • Wiehe JM et al (2013) GMP-adapted overexpression of CXCR4 in human mesenchymal stem cells for cardiac repair. International journal of cardiology 167(5):2073–2081

    Google Scholar 

  • Wilson JG et al (2015) Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med 3(1):24–32

    Article  Google Scholar 

  • Yamahara K et al (2014) Comparison of angiogenic, cytoprotective, and immunosuppressive properties of human amnion-and chorion-derived mesenchymal stem cells. PloS one 9(2):e88319

    Google Scholar 

  • Yang C et al (2018) Theranostic niosomes for efficient siRNA/MicroRNA delivery and activatable near-infrared fluorescent tracking of stem cells. ACS applied materials & interfaces 10(23):19494–19503

    Google Scholar 

  • Yu X et al (2012) Overexpression of CXCR4 in mesenchymal stem cells promotes migration, neuroprotection and angiogenesis in a rat model of stroke. Journal of the neurological sciences 316(1–2):141–149

    Google Scholar 

  • Yu B et al (2016) Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1. Scientific reports 6:34562

    Google Scholar 

  • Yu M et al (2017) Optimizing surface-engineered ultra-small gold nanoparticles for highly efficient miRNA delivery to enhance osteogenic differentiation of bone mesenchymal stromal cells. Nano Research 10(1):49–63

    Google Scholar 

  • Zhao M-Z et al (2006) Novel therapeutic strategy for stroke in rats by bone marrow stromal cells and ex vivo HGF gene transfer with HSV-1 vector. Journal of Cerebral Blood Flow & Metabolism 26(9):1176–1188

    Google Scholar 

  • Zhao L et al (2016) Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction. Experimental cell research 344(1):30–39

    Google Scholar 

  • Zhao Y et al (2017) Targeted delivery of doxorubicin by nano-loaded mesenchymal stem cells for lung melanoma metastases therapy. Sci Rep 7:44758

    Article  CAS  Google Scholar 

  • Zheng L et al (2012) Antitumor activities of human placenta-derived mesenchymal stem cells expressing endostatin on ovarian cancer. PloS one 7(7):e39119

    Google Scholar 

  • Zhu YG et al (2014) Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem cells 32(1):116–125

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Basic Sciences, The American University of Antigua-College of Medicine, Coolidge, Antigua and Barbuda

    Noha Attia

  2. The Center of research and evaluation, The American University of Antigua-College of Medicine, Coolidge, Antigua and Barbuda

    Noha Attia & Mohamed Mashal

  3. Histology and Cell Biology Department, Faculty of Medicine, University of Alexandria, Alexandria, Egypt

    Noha Attia

  4. NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain

    Noha Attia & Mohamed Mashal

Authors
  1. Noha Attia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohamed Mashal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Noha Attia .

Editor information

Editors and Affiliations

  1. (emeritus), Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Kursad Turksen

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Attia, N., Mashal, M. (2020). Mesenchymal Stem Cells: The Past Present and Future. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 11. Advances in Experimental Medicine and Biology(), vol 1312. Springer, Cham. https://doi.org/10.1007/5584_2020_595

Download citation

Publish with us

Policies and ethics

Search

Navigation