Amalgamation of Stem Cells with Nanotechnology: A Unique Therapeutic Approach

Author(s): Amit Alexander, Shailendra Saraf*, Swarnlata Saraf, Mukta Agrawal, Ravish J. Patel, Palak Agrawal, Junaid Khan, Ajazuddin

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 2 , 2019

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In the last few years, the stem cell therapy has gained much popularity among researchers and scientists of biomedical field. It became an effective and alternative approach for the treatment of various physiological conditions (like accidental injuries, burn damage, organ failure, bone marrow transfusion, etc.) and chronic disorders (diabetes, cancer, neurodegenerative disorders, periodontal diseases, etc.). Due to the unique ability of cellular differentiation and regeneration, stem cell therapy serves as the last hope for various incurable conditions and severe damages. The amalgamation of stem cell therapy with nanotechnology brings new prospects to the stem cell research, as it improves the specificity of the treatment and controls the stem cell proliferation and differentiation. In this review article, we have discussed various nanocarrier systems such as carbon nanotubes, quantum dots, nanofibers, nanoparticles, nanodiamonds, nanoparticle scaffold, etc. utilized for the delivery of stem cell inside the body.

Keywords: Stem cell, nanotechnology, pluripotency, tissue repair, tissue engineering, therapeutic approach.

Gholizadeh-Ghaleh AS, Gholizadeh-Ghaleh AS, Akbarzadeh A. The potential of nanofibers in tissue engineering and stem cell therapy. Artif Cells Nanomed Biotechnol 2016; 44(5): 1195-200.
Gotoh N. Control of stemness by fibroblast growth factor signaling in stem cells and cancer stem cells. Curr Stem Cell Res Ther 2009; 4(1): 9-15.
Zhou Y, Chakravorty N, Xiao Y, Gu W. Mesenchymal stem cells and nano-structured surfaces. Methods Mol Biol 2013; 1058: 133-48.
Chenchen Z, Brian EG, Shujuan Z. Regulators of stem cells proliferation in tissue regeneration. Curr Stem Cell Res Ther 2016; 11(3): 177-87.
Sadhukha T, O’Brien TD, Prabha S. Nano-engineered mesenchymal stem cells as targeted therapeutic carriers. J Control Release 2014; 196: 243-51.
Sun Z, Wang S, Zhao RC. The roles of mesenchymal stem cells in tumor inflammatory microenvironment. J Hematol Oncol 2014; 7: 14.
Rada T, Reis RL, Gomes ME. Adipose tissue-derived stem cells and their application in bone and cartilage tissue engineering. Tissue Eng Part B Rev 2009; 15(2): 113-25.
Xia L, Lin K, Jiang X, et al. Effect of nano-structured bioceramic surface on osteogenic differentiation of adipose derived stem cells. Biomaterials 2014; 35(30): 8514-27.
Levi B, Longaker MT. Concise review: Adipose-derived stromal cells for skeletal regenerative medicine. Stem Cells (Dayton, Ohio) 2011; 29(4): 576-82.
Anuruthran A, James Min-Leong W, Wasim SK. Preclinical and Clinical Studies on the Use of Stem Cells for Bone Repair: A Systematic Review. Curr Stem Cell Res Ther 2013; 8(3): 210-6.
Mashinchian O, Turner LA, Dalby MJ, et al. Regulation of stem cell fate by nanomaterial substrates. Nanomedicine (Lond) 2015; 10(5): 829-47.
Bianco P. Bone and the hematopoietic niche: A tale of two stem cells. Blood 2011; 117(20): 5281-8.
Ehninger A, Trumpp A. The bone marrow stem cell niche grows up: Mesenchymal stem cells and macrophages move in. J Exp Med 2011; 208(3): 421-8.
Petek K, Sevil K, Cagla Zubeyde K. Biomaterial and stem cell interactions: Histological biocompatibility. Curr Stem Cell Res Ther 2016; 11(6): 475-86.
Cosson S, Otte EA, Hezaveh H, Cooper-White JJ. Concise review: Tailoring bioengineered scaffolds for stem cell applications in tissue engineering and regenerative medicine. Stem Cells Transl Med 2015; 4(2): 156-64.
Adams GB, Chabner KT, Alley IR, et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature 2006; 439(7076): 599-603.
McMurray RJ, Gadegaard N, Tsimbouri PM, et al. Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency. Nat Mater 2011; 10(8): 637-44.
Yanes O, Clark J, Wong DM, et al. Metabolic oxidation regulates embryonic stem cell differentiation. Nat Chem Biol 2010; 6(6): 411-7.
Fatima F, Nawaz M. Stem cell-derived exosomes: Roles in stromal remodeling, tumor progression, and cancer immunotherapy. Chin J Cancer 2015; 34(12): 541-53.
Jaggupilli A, Elkord E. Significance of CD44 and CD24 as cancer stem cell markers: An enduring ambiguity. Clin Dev Immunol 2012; 2012: 708036.
Xia P. Surface markers of cancer stem cells in solid tumors. Curr Stem Cell Res Ther 2014; 9(2): 102-11.
Jewett A, Tseng HC, Arasteh A, Saadat S, Christensen RE, Cacalano NA. Natural killer cells preferentially target cancer stem cells; role of monocytes in protection against NK cell mediated lysis of cancer stem cells. Curr Drug Deliv 2012; 9(1): 5-16.
Kingham E, Oreffo RO. Embryonic and induced pluripotent stem cells: understanding, creating, and exploiting the nano-niche for regenerative medicine. ACS Nano 2013; 7(3): 1867-81.
Feyzan Ozdal K, Hafize Seda V. Potential clinical use of differentiated cells from embryonic or mesencyhmal stem cells in orthopaedic problems. Curr Stem Cell Res Ther 2016; 11(6): 522-9.
Ghanian MH, Farzaneh Z, Barzin J, et al. Nanotopographical control of human embryonic stem cell differentiation into definitive endoderm. J Biomed Mater Res A 2015; 103(11): 3539-53.
Schwartz RE, Fleming HE, Khetani SR, Bhatia SN. Pluripotent stem cell-derived hepatocyte-like cells. Biotechnol Adv 2014; 32(2): 504-13.
Sneddon JB, Borowiak M, Melton DA. Self-renewal of embryonic-stem-cell-derived progenitors by organ-matched mesenchyme. Nature 2012; 491(7426): 765-8.
Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels. Science (New York, NY) 2001; 294(5542): 564-7.
Wessells NK, Cohen JH. Early pancreas organogenesis: Morphogenesis, tissue interactions, and mass effects. Dev Biol 1967; 15(3): 237-70.
Golosow N, Grobstein C. Epitheliomesenchymal interaction in pancreatic morphogenesis. Dev Biol 1962; 4: 242-55.
Jung Y, Brack AS. Cellular mechanisms of somatic stem cell aging. Curr Top Dev Biol 2014; 107: 405-38.
Goodell MA, Nguyen H, Shroyer N. Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments. Nat Rev Mol Cell Biol 2015; 16(5): 299-309.
Jeong Y, Choi J, Lee KH. Technology advancement for integrative stem cell analyses. Tissue Eng Part B Rev 2014; 20(6): 669-82.
Davidson KC, Adams AM, Goodson JM, et al. Wnt/beta-catenin signaling promotes differentiation, not self-renewal, of human embryonic stem cells and is repressed by Oct4. Proc Natl Acad Sci USA 2012; 109(12): 4485-90.
Tan J, Xu X, Lin J, Fan L, Zheng Y, Kuang W. Dental stem cell in tooth development and advances of adult dental stem cell in regenerative therapies. Curr Stem Cell Res Ther 2015; 10(5): 375-83.
Kerativitayanan P, Carrow JK, Gaharwar AK. Nanomaterials for engineering stem cell responses. Adv Healthc Mater 2015; 4(11): 1600-27.
Andre EM, Passirani C, Seijo B, Sanchez A, Montero-Menei CN. Nano and microcarriers to improve stem cell behaviour for neuroregenerative medicine strategies: Application to Huntington’s disease. Biomaterials 2016; 83: 347-62.
Singer K, DelProposto J, Morris DL, et al. Diet-induced obesity promotes myelopoiesis in hematopoietic stem cells. Mol Metab 2014; 3(6): 664-75.
Suad A, Patrick RJF, Ernst W. Advances in Reprogramming to Pluripotency. Curr Stem Cell Res Ther 2015; 10(3): 193-207.
Berna K, Sevil K, Petek K, Muharrem T, Feza K. Mesenchymal stem cells and nano-bioceramics for bone regeneration. Curr Stem Cell Res Ther 2016; 11(6): 487-93.
Mahla RS. Stem cells applications in regenerative medicine and disease therapeutics. Int J Cell Biol 2016; 2016: 6940283.
Ferreira L, Karp JM, Nobre L, Langer R. New opportunities: The use of nanotechnologies to manipulate and track stem cells. Cell Stem Cell 2008; 3(2): 136-46.
Kutsuzawa K, Akaike T, Chowdhury EH. The influence of the cell-adhesive proteins E-cadherin and fibronectin embedded in carbonate-apatite DNA carrier on transgene delivery and expression in a mouse embryonic stem cell line. Biomaterials 2008; 29(3): 370-6.
Slotkin JR, Chakrabarti L, Dai HN, et al. In vivo quantum dot labeling of mammalian stem and progenitor cells. Dev Dyn 2007; 236(12): 3393-401.
Arora P, Sindhu A, Dilbaghi N, Chaudhury A, Rajakumar G, Rahuman AA. Nano-regenerative medicine towards clinical outcome of stem cell and tissue engineering in humans. J Cell Mol Med 2012; 16(9): 1991-2000.
Wang Z, Ruan J, Cui D. Advances and prospect of nanotechnology in stem cells. Nanoscale Res Lett 2009; 4(7): 593-605.
Bruchez M Jr, Moronne M, Gin P, Weiss S, Alivisatos AP. Semiconductor nanocrystals as fluorescent biological labels. Science (New York, NY) 1998; 281(5385): 2013-6.
Michalet X, Pinaud FF, Bentolila LA, et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science (New York, NY) 2005; 307(5709): 538-44.
Chen H, Titushkin I, Stroscio M, Cho M. Altered membrane dynamics of quantum dot-conjugated integrins during osteogenic differentiation of human bone marrow derived progenitor cells. Biophys J 2007; 92(4): 1399-408.
Chakraborty SK, Fitzpatrick JA, Phillippi JA, et al. Cholera toxin B conjugated quantum dots for live cell labeling. Nano Lett 2007; 7(9): 2618-26.
Rota M, Kajstura J, Hosoda T, et al. Bone marrow cells adopt the cardiomyogenic fate in vivo. Proc Natl Acad Sci USA 2007; 104(45): 17783-8.
Lu CW, Hung Y, Hsiao JK, et al. Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. Nano Lett 2007; 7(1): 149-54.
Gupta AK, Curtis AS. Lactoferrin and ceruloplasmin derivatized superparamagnetic iron oxide nanoparticles for targeting cell surface receptors. Biomaterials 2004; 25(15): 3029-40.
Reimer P, Balzer T. Ferucarbotran (Resovist): A new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications. Eur Radiol 2003; 13(6): 1266-76.
Zhu J, Zhou L. XingWu F. Tracking neural stem cells in patients with brain trauma. N Engl J Med 2006; 355(22): 2376-8.
David AS. Recent advancements in carbon nanofiber and carbon nanotube applications in drug delivery and tissue engineering. Curr Pharm Des 2015; 21(15): 2037-44.
Ramon-Azcon J, Ahadian S, Obregon R, Shiku H, Ramalingam M, Matsue T. Applications of carbon nanotubes in stem cell research. J Biomed Nanotechnol 2014; 10(10): 2539-61.
Melita ED, Purcel G, Grumezescu AM. Carbon nanotubes for cancer therapy and neurodegenerative diseases. Rom J Morphol Embryol 2015; 56(2): 349-56.
Qin L-C, Zhao X, Hirahara K, Miyamoto Y, Ando Y, Iijima S. The smallest carbon nanotube. Nature 2000; 408: 50.
Whitlow J, Pacelli S, Paul A. Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions. J Control Release 2017; 261: 62-86.
Pacelli S, Maloney R, Chakravarti AR, et al. Controlling adult stem cell behavior using nanodiamond-reinforced hydrogel: Implication in bone regeneration therapy. Sci Rep 2017; 7(1): 6577.
Taylor AC, González CH, Miller BS, Edgington RJ, Ferretti P, Jackman RB. Surface functionalisation of nanodiamonds for human neural stem cell adhesion and proliferation. Sci Rep 2017; 7(1): 7307.
Iakoubovskii K, Baidakova MV, Wouters BH, et al. Structure and defects of detonation synthesis nanodiamond. Diamond Related Materials 2000; 9(3): 861-5.
Ansari SA, Satar R, Jafri MA, Rasool M, Ahmad W, Kashif ZS. Role of nanodiamonds in drug delivery and stem cell therapy. Iranian J Biotechnol 2016; 14(3): 130-41.
Lin C, Yong Z, Yuemin N, Liang Q. Induced Pluripotent Stem Cells (iPSCs) in the Modeling of Hepatitis C Virus Infection. Curr Stem Cell Res Ther 2015; 10(3): 216-9.
Lam R, Chen M, Pierstorff E, Huang H, Osawa E, Ho D. Nanodiamond-embedded microfilm devices for localized chemotherapeutic elution. ACS Nano 2008; 2(10): 2095-102.
Puzyr AP, Baron AV, Purtov KV, et al. Nanodiamonds with novel properties: A biological study. Diamond Related Materials 2007; 16(12): 2124-8.
Mooney DJ, Vandenburgh H. Cell delivery mechanisms for tissue repair. Cell Stem Cell 2008; 2(3): 205-13.
Dzenis Y. Material science. Spinning continuous fibers for nanotechnology. Science (New York, NY) 2004; 304(5679): 1917-9.
Silva GA, Czeisler C, Niece KL, et al. Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science (New York, NY) 2004; 303(5662): 1352-5.
Shih YR, Chen CN, Tsai SW, Wang YJ, Lee OK. Growth of mesenchymal stem cells on electrospun type I collagen nanofibers. Stem Cells (Dayton, Ohio) 2006; 24(11): 2391-7.
Nur EKA, Ahmed I, Kamal J, Schindler M, Meiners S. Three-dimensional nanofibrillar surfaces promote self-renewal in mouse embryonic stem cells. Stem Cells (Dayton, Ohio) 2006; 24(2): 426-33.
Yang F, Murugan R, Wang S, Ramakrishna S. Electrospinning of nano/micro scale poly (L-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials 2005; 26(15): 2603-10.
Hashi CK, Zhu Y, Yang GY, et al. Antithrombogenic property of bone marrow mesenchymal stem cells in nanofibrous vascular grafts. Proc Natl Acad Sci USA 2007; 104(29): 11915-20.
Narayanan K, Mishra S, Singh S, Pei M, Gulyas B, Padmanabhan P. Engineering concepts in stem cell research. Biotechnol J 2017; 12(12)
Kuraitis D, Ruel M, Suuronen EJ. Mesenchymal stem cells for cardiovascular regeneration. Cardiovasc Drugs Ther 2011; 25(4): 349-62.
Kaur S, Singhal B. When nano meets stem: the impact of nanotechnology in stem cell biology. J Biosci Bioeng 2012; 113(1): 1-4.
Mooney E, Dockery P, Greiser U, Murphy M, Barron V. Carbon nanotubes and mesenchymal stem cells: Biocompatibility, proliferation and differentiation. Nano Lett 2008; 8(8): 2137-43.
Jing Y, Moore LR, Williams PS, et al. Blood progenitor cell separation from clinical leukapheresis product by magnetic nanoparticle binding and magnetophoresis. Biotechnol Bioeng 2007; 96(6): 1139-54.
Jing M, Liu XQ, Liang P, Li CY, et al. Labeling neural stem cells with superparamagnetic iron oxide in vitro and tracking after implantation with MRI in vivo. Zhonghua Yi Xue Za Zhi 2004; 84(16): 1386-9.
Ohyabu Y, Kaul Z, Yoshioka T, et al. Stable and nondisruptive in vitro/in vivo labeling of mesenchymal stem cells by internalizing quantum dots. Hum Gene Ther 2009; 20(3): 217-24.
Pickard MR, Barraud P, Chari DM. The transfection of multipotent neural precursor/stem cell transplant populations with magnetic nanoparticles. Biomaterials 2011; 32(9): 2274-84.
Chen D, Tang Q, Xue W, Wang X. The feasibility of using magnetic nanoparticles modified as gene vector. West Indian Med J 2010; 59(3): 300-5.
Kim JH, Park JS, Yang HN, et al. The use of biodegradable PLGA nanoparticles to mediate SOX9 gene delivery in human mesenchymal stem cells (hMSCs) and induce chondrogenesis. Biomaterials 2011; 32(1): 268-78.
Ruan J, Shen J, Wang Z, et al. Efficient preparation and labeling of human induced pluripotent stem cells by nanotechnology. Int J Nanomedicine 2011; 6: 425-35.
Ghosh SK, Pal T. Photophysical aspects of molecular probes near nanostructured gold surfaces. Phys Chem Chem Phys 2009; 11(20): 3831-44.
Kim JH, Lee S, Park K, et al. Protein-phosphorylation-responsive polymeric nanoparticles for imaging protein kinase activities in single living cells. Angew Chem Int Ed Engl 2007; 46(30): 5779-82.
Liu Q, Huang H, Cai H, et al. Embryonic stem cells as a novel cell source of cell-based biosensors. Biosens Bioelectron 2007; 22(6): 810-5.
Paul A, Manoharan V, Krafft D, et al. Nanoengineered biomimetic hydrogels for guiding human stem cell osteogenesis in three dimensional microenvironments. J Mater Chem B 2016; 4(20): 3544-54.
Tasoglu S, Gurkan UA, Wang S, Demirci U. Manipulating biological agents and cells in micro-scale volumes for applications in medicine. Chem Soc Rev 2013; 42(13): 5788-808.
Guldris N, Argibay B, Gallo J. Magnetite nanoparticles for stem cell labeling with high efficiency and long-term in vivo tracking. Bioconjug Chem 2017; 28(2): 362-70.
Freeman FE, Kelly DJ. Tuning alginate bioink stiffness and composition for controlled growth factor delivery and to spatially direct msc fate within bioprinted tissues. Sci Rep 2017; 7(1): 17042.
Apelgren P, Amoroso M, Lindahl A, et al. Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo. PLoS One 2017; 12(12): e0189428.

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Article Details

Year: 2019
Published on: 03 July, 2018
Page: [83 - 92]
Pages: 10
DOI: 10.2174/1574888X13666180703143219
Price: $65

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