Magnetically actuated microrobots as a platform for stem cell transplantation

Magnetic microrobots developed for 3D culture and precise delivery of cells were successfully controlled in various environments. Magnetic microrobots were developed for three-dimensional culture and the precise delivery of stem cells in vitro, ex vivo, and in vivo. Hippocampal neural stem cells attached to the microrobots proliferated and differentiated into astrocytes, oligodendrocytes, and neurons. Moreover, microrobots were used to transport colorectal carcinoma cancer cells to tumor microtissue in a body-on-a-chip, which comprised an in vitro liver-tumor microorgan network. The microrobots were also controlled in a mouse brain slice and rat brain blood vessel. Last, microrobots carrying mesenchymal stem cells derived from human nose were manipulated inside the intraperitoneal cavity of a nude mouse. The results indicate the potential of microrobots for the culture and delivery of stem cells.

[1]  J. Chae,et al.  In Vitro Hydrodynamic, Transient, and Overtime Performance of a Miniaturized Valve for Hydrocephalus , 2015, Annals of Biomedical Engineering.

[2]  H. Tse,et al.  Mesenchymal stem cells and immunomodulation: current status and future prospects , 2016, Cell Death and Disease.

[3]  M. Kassem,et al.  The Human Umbilical Cord Blood: A Potential Source for Osteoblast Progenitor Cells , 2003, Calcified Tissue International.

[4]  Benedikt F. Seitz,et al.  Undulatory Locomotion of Magnetic Multilink Nanoswimmers. , 2015, Nano letters.

[5]  Three-dimensional spheroid culture targeting versatile tissue bioassays using a PDMS-based hanging drop array , 2017, Scientific Reports.

[6]  Li Zhang,et al.  Fabrication and Manipulation of Ciliary Microrobots with Non-reciprocal Magnetic Actuation , 2016, Scientific Reports.

[7]  W S Oetting,et al.  A second locus for familial high myopia maps to chromosome 12q. , 1998, American journal of human genetics.

[8]  J. Goudreau,et al.  Autophagic Death of Adult Hippocampal Neural Stem Cells Following Insulin Withdrawal , 2008, Stem cells.

[9]  Li Zhang,et al.  Bio-inspired magnetic swimming microrobots for biomedical applications. , 2013, Nanoscale.

[10]  D. Prockop,et al.  Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. , 2006, Cytotherapy.

[11]  S. Martel,et al.  Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions , 2016, Nature nanotechnology.

[12]  Jiangnan Yu,et al.  Nasal ectomesenchymal stem cells: multi-lineage differentiation and transformation effects on fibrin gels. , 2015, Biomaterials.

[13]  Jake J. Abbott,et al.  How Should Microrobots Swim? , 2009 .

[14]  Yang Jun Kang,et al.  Changes in velocity profile according to blood viscosity in a microchannel. , 2014, Biomicrofluidics.

[15]  S. Misra,et al.  MagnetoSperm: A microrobot that navigates using weak magnetic fields , 2014 .

[16]  Krzysztof K. Krawczyk,et al.  Magnetic Helical Micromachines: Fabrication, Controlled Swimming, and Cargo Transport , 2012, Advanced materials.

[17]  Ali A. Qadeer,et al.  Estimating Lengths of Semitendinosus and Gracilis Tendons by Magnetic Resonance Imaging. , 2018, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[18]  D. Wiersma,et al.  Structured light enables biomimetic swimming and versatile locomotion of photoresponsive soft microrobots. , 2016, Nature materials.

[19]  O. Lindvall,et al.  Stem cell therapy for human neurodegenerative disorders–how to make it work , 2004, Nature Medicine.

[20]  F. Qiu,et al.  Controlled In Vivo Swimming of a Swarm of Bacteria‐Like Microrobotic Flagella , 2015, Advanced materials.

[21]  Franziska Ullrich,et al.  Mobility experiments with microrobots for minimally invasive intraocular surgery. , 2013, Investigative ophthalmology & visual science.

[22]  Y. Sheng,et al.  Glial differentiation of human inferior turbinate-derived stem cells: a new source of cells for nerve repair , 2017, Neuroreport.

[23]  C. Don,et al.  Human embryonic stem cell–derived cardiomyocytes restore function in infarcted hearts of non-human primates , 2018 .

[24]  Jake J. Abbott,et al.  Modeling Magnetic Torque and Force for Controlled Manipulation of Soft-Magnetic Bodies , 2007, IEEE Transactions on Robotics.

[25]  J. Schulz-Menger,et al.  Myocardial effective transverse relaxation time T2* Correlates with left ventricular wall thickness: A 7.0 T MRI study , 2017, Magnetic resonance in medicine.

[26]  T. Bonfield,et al.  Concise Review: Mesenchymal Stem Cell Therapy for Pediatric Disease: Perspectives on Success and Potential Improvements. , 2016, Stem Cells Translational Medicine.

[27]  G. Sukhikh,et al.  Mesenchymal Stem Cells , 2002, Bulletin of Experimental Biology and Medicine.

[28]  L. Gaitini,et al.  Inferior Turbinectomy versus Submucosal Diathermy for Inferior Turbinate Hypertrophy , 2000, The Annals of otology, rhinology, and laryngology.

[29]  Y. Toh,et al.  Substrate stiffness modulates the multipotency of human neural crest derived ectomesenchymal stem cells via CD44 mediated PDGFR signaling. , 2018, Biomaterials.

[30]  Yu Jin Jang,et al.  ACT-PRESTO: Rapid and consistent tissue clearing and labeling method for 3-dimensional (3D) imaging , 2016, Scientific Reports.

[32]  Dong-Woo Cho,et al.  Human Inferior Turbinate , 2012, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[33]  A. Storch,et al.  Tissue-Specific Progenitor and Stem Cells Intrastriatal Transplantation of Adult Human Neural Crest-Derived Stem Cells Improves Functional Outcome in Parkinsonian Rats , 2014 .

[34]  Metin Sitti,et al.  Miniature devices: Voyage of the microrobots , 2009, Nature.

[35]  A. Rumley,et al.  Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study , 1997, British journal of haematology.

[36]  T. Shimazaki,et al.  [Mammalian neural stem cells]. , 2008, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[37]  B. Nelson,et al.  3D Fabrication of Fully Iron Magnetic Microrobots. , 2019, Small.

[38]  Jeong-Woo Choi,et al.  Phototactic guidance of a tissue-engineered soft-robotic ray , 2016, Science.

[39]  Salvador Pané,et al.  Polymer-Based Wireless Resonant Magnetic Microrobots , 2014, IEEE Trans. Robotics.

[40]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[41]  Malin Parmar,et al.  Human Trials of Stem Cell-Derived Dopamine Neurons for Parkinson's Disease: Dawn of a New Era. , 2017, Cell stem cell.

[42]  Dong Chang Lee,et al.  Age-Related Characteristics of Multipotent Human Nasal Inferior Turbinate-Derived Mesenchymal Stem Cells , 2013, PloS one.

[43]  Ioannis K. Kaliakatsos,et al.  Microrobots for minimally invasive medicine. , 2010, Annual review of biomedical engineering.

[44]  Li Zhang,et al.  Fabrication and Characterization of Magnetic Microrobots for Three-Dimensional Cell Culture and Targeted Transportation , 2013, Advanced materials.

[45]  B. Nelson,et al.  Microrobots: a new era in ocular drug delivery , 2014, Expert opinion on drug delivery.

[46]  Metin Sitti,et al.  Soft erythrocyte-based bacterial microswimmers for cargo delivery , 2018, Science Robotics.

[47]  Soichiro Tottori,et al.  Magnetic helical micromachines. , 2013, Chemistry.

[48]  Marcus L. Roper,et al.  Microscopic artificial swimmers , 2005, Nature.

[49]  Ran Wang,et al.  Development of a magnetic microrobot for carrying and delivering targeted cells , 2018, Science Robotics.

[50]  Max T. Hou,et al.  Development of rolling magnetic microrobots , 2010 .

[51]  Sukho Park,et al.  Development of Biomedical Microrobot for Intravascular Therapy , 2010 .

[52]  T. Palmer,et al.  Fibroblast Growth Factor-2 Activates a Latent Neurogenic Program in Neural Stem Cells from Diverse Regions of the Adult CNS , 1999, The Journal of Neuroscience.

[53]  R. Rosenson,et al.  Distribution of blood viscosity values and biochemical correlates in healthy adults. , 1994, Clinical chemistry.

[54]  Mariana Medina-Sánchez,et al.  Medical microbots need better imaging and control , 2017, Nature.

[55]  A. Forgione In vivo microrobots for natural orifice transluminal surgery. Current status and future perspectives. , 2009, Surgical oncology.

[56]  Hongsoo Choi,et al.  Noncytotoxic artificial bacterial flagella fabricated from biocompatible ORMOCOMP and iron coating. , 2014, Journal of materials chemistry. B.

[57]  Lil Pabon,et al.  Human ESC-Derived Cardiomyocytes Restore Function in Infarcted Hearts of Non-Human Primates , 2018, Nature Biotechnology.

[58]  Salvador Pané,et al.  Polymer-based Wireless Resonant Magnetic microrobots , 2012, 2012 IEEE International Conference on Robotics and Automation.

[59]  Jake J. Abbott,et al.  Robotics in the Small, Part I: Microbotics , 2007, IEEE Robotics & Automation Magazine.

[60]  Oliver Lieleg,et al.  Enzymatically active biomimetic micropropellers for the penetration of mucin gels , 2015, Science Advances.

[61]  Zhijian Zhang,et al.  Rat Nasal Respiratory Mucosa-Derived Ectomesenchymal Stem Cells Differentiate into Schwann-Like Cells Promoting the Differentiation of PC12 Cells and Forming Myelin In Vitro , 2015, Stem cells international.

[62]  Xiaomiao Feng,et al.  Bioinspired helical microswimmers based on vascular plants. , 2014, Nano letters.

[63]  D. Muller,et al.  A simple method for organotypic cultures of nervous tissue , 1991, Journal of Neuroscience Methods.

[64]  Jake J. Abbott,et al.  How Should Microrobots Swim? , 2009, ISRR.

[65]  D. Cho,et al.  Human turbinate mesenchymal stromal cell sheets with bellows graft for rapid tracheal epithelial regeneration. , 2015, Acta biomaterialia.

[66]  Sukho Park,et al.  A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair , 2017, Advanced healthcare materials.

[67]  F. Gage,et al.  Isolation, characterization, and use of stem cells from the CNS. , 1995, Annual review of neuroscience.

[68]  Shinya Yamanaka,et al.  Induced pluripotent stem cell technology: a decade of progress , 2016, Nature Reviews Drug Discovery.

[69]  Fred H. Gage,et al.  The Adult Rat Hippocampus Contains Primordial Neural Stem Cells , 1997, Molecular and Cellular Neuroscience.

[70]  Hongsoo Choi,et al.  A Capsule‐Type Microrobot with Pick‐and‐Drop Motion for Targeted Drug and Cell Delivery , 2018, Advanced healthcare materials.

[71]  Kyung-Ok Cho,et al.  Therapeutic Potential of Human Turbinate-Derived Mesenchymal Stem Cells in Experimental Acute Ischemic Stroke , 2018, International neurourology journal.

[72]  J. Rhie,et al.  Induction of chondrogenic differentiation in cultured fibroblasts isolated from the inferior turbinate , 2008, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[73]  Bradley J. Nelson,et al.  Biological Cell Injection Using an Autonomous MicroRobotic System , 2002, Int. J. Robotics Res..

[74]  A. Caplan,et al.  Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5‐azacytidine , 1995, Muscle & nerve.

[75]  E. Purcell Life at Low Reynolds Number , 2008 .