Development of in vivo stem cell monitoring technology

A domestic research team has developed a stem cell biometric monitoring system based on magnetic resonance imaging for the purpose of effective stem cell treatment. The human stem cell monitoring strategy is expected to contribute significantly to the development of effective stem cell treatment strategies in the future.

Stem cells have been in the spotlight now and in the past. Source: AdobeStock

Dr. Eun-kyung Lim of the Bio-Nano Research Center at the Korea Research Institute of Bioscience and Biotechnology was published in’Biosensors and Bioelectronics’ in collaboration with Professor Seung-Joo Ham’s team of Department of Chemical and Biotechnology of Yonsei University, and Professor Yoo-Min Yoo’s team of Department of Radiology (correspondence).

Confirmation of stem cells transplanted in vivo

Since stem cells can differentiate and self-reproduce into various cells, there are many studies on stem cell therapeutics that use them to regenerate and treat damaged tissues or organs. Among stem cells, induced pluripotent stem cells are cells that can differentiate into all organs of the body, and can be made by dedifferentiating the somatic cells of an adult human body. Induced pluripotent stem cells are in the spotlight as cells that have similar abilities to embryonic stem cells, but can solve the problem of immune rejection by inducing the ethical problems of embryonic stem cells that are produced while destroying embryonic cells and by dedifferentiating patient somatic cells. .

Schematic diagram of an MR image-based human stem cell monitoring system using hollow MnO nanoparticles (MnOHo-Ab) targeting specific integrins. MnOHo-Ab can target and monitor differentiated human stem cells from all lineages after transplantation. Source: Korea Research Institute of Bioscience and Biotechnology

Adult stem cells derived from induced pluripotent stem cells have been studied to improve the therapeutic effect by inducing differentiation into specific cells with limited proliferation and low migration rate. In addition, since only 1~2% of induced stem cells reach the target tissue and the rest is lost, it was necessary to verify the effect of stem cell differentiation treatment.

Confirmation of MnOHo-Ab production for monitoring human stem cell transplantation in vivo. a) Transmission electron microscope image of MnOHo-Ab particles. b) Confirmation of magnetization degree of MnOHo-Ab c) Confirmation of T1/T2 emphasis image by MnOHo-Ab concentration. Source: Korea Research Institute of Bioscience and Biotechnology

The research team developed special manganese nanoparticles and applied them to manufacture’Integrin β1 Antibody (MnOHo-Ab)’, which enables target monitoring of stem cells. In addition, we developed a method for minimally invasive monitoring of human stem cells transplanted preclinically using a magnetic resonance imaging device.

It is a marker that targets integrin β1 expressed in stem cell lineages and enables target monitoring regardless of the stage of stem cell differentiation.

The research team confirmed that’integrin β1-manganese nanoparticles (MnOHo-Ab)’ injected into a vein can be transferred to the mouse testis, allowing monitoring of human induced pluripotent stem cells (hiPSCs) differentiated into various lineages.

Optimization of the imaging time of MnOHo-Ab to monitor human stem cell transplantation in vivo. a) In vivo T1 weighted MR images at various times (before injection: before injection, immediately: immediately after injection and 1, 2 and 4 hours after injection) after intravenous injection of MnOHo-Ab and MnOHo; The area within the red dotted line is the hiPSCs-induced teratoma area. b) Relative T1 signal intensity (%) of the red dotted area of the MRI image in a) (signal intensity (%) = ΔR / RNT, where ΔR = R-RNT); Red and blue bars represent MnOHo-Ab and MnOHO, respectively. Source: Korea Research Institute of Bioscience and Biotechnology — Optimization of the imaging time of MnOHo-Ab to monitor human stem cell transplantation in vivo. a) In vivo T1 weighted MR images at various times (before injection: before injection, immediately: immediately after injection and 1, 2 and 4 hours after injection) after intravenous injection of MnOHo-Ab and MnOHo; The area within the red dotted line is the hiPSCs-induced teratoma area. b) Relative T1 signal intensity (%) of the red dotted region of the MRI image in a) (signal intensity (%) = ΔR / RNT, where ΔR = R-RNT); Red and blue bars represent MnOHo-Ab and MnOHO, respectively. Source: Korea Research Institute of Bioscience and Biotechnology

The biometric monitoring technology developed this time shows whether the injected human stem cells have been transferred and transplanted to the target site for a long period of time to be treated.

Monitoring of human stem cell transplantation of MnOHo-Ab at the preclinical level. a) MnOHo-Ab was administered to mice with a constant MRI period for monitoring stem cell transplantation using MnOHo-Ab. MRI images were checked weekly after transplanting hiPSCs into mouse testis. b) In vivo T1-weighted MRI image after intravenous injection of MnOHo-Ab (2 mg Mn per injection) and c) Relative T1 signal intensity (signal intensity (%) = ΔR/Rpre, where ΔR = R-Rpre) area of red dashed line . Orange and red bars represent T1 signal intensity at pre-injection and 2 hours post-injection, respectively. Source: Korea Research Institute of Bioscience and Biotechnology

“In the field of regenerative medicine using stem cells,” said Dr. Eunkyung Lim, the research director, “It is an excellent point that the transplantation and migration of stem cells in the preclinical model to the target disease site can be visually verified using magnetic resonance imaging technology.” The achievement is the development of an imaging platform that can confirm whether the stem cells injected into the body have been well delivered to the target cells and whether the stem cell treatment is progressing in the future. “I said.

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