Rapid generation of OPC-like cells from human pluripotent stem cells for treating spinal cord injury

• Published in: Experimental & molecular medicine Vol. 49; no. 7; p. e361
• Main Authors: Kim, Dae-Sung, Jung, Se Jung, Lee, Jae Souk, Lim, Bo Young, Kim, Hyun Ah, Yoo, Jeong-Eun, Kim, Dong-Wook, Leem, Joong Woo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-07-2017; Springer Nature B.V; Nature Publishing Group
• Subjects: 13; 13/100; 631/378/1687/1825; 631/532/1360; 631/532/489; Animal models; Animals; Antigens - metabolism; Axons - metabolism; Behavior Rating Scale; Biomedical and Life Sciences; Biomedicine; Cell Differentiation; Cell Line; Cells, Cultured; Conduction; Disease Models, Animal; Glial stem cells; Growth factors; Hindlimb; Humans; Insulin; Insulin-like growth factor I; Male; Medical Biochemistry; Molecular Medicine; Motor task performance; Myelin Sheath - physiology; Myelination; Neural stem cells; Oligodendrocyte Precursor Cells - cytology; Oligodendrocyte Precursor Cells - transplantation; Original; original-article; Platelet-derived growth factor; Pluripotency; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - transplantation; Proteoglycans - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Rodents; Spinal cord injuries; Spinal Cord Injuries - surgery; Stem cell transplantation; Stem Cells; Thorax; Time Factors; Transplantation
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/emm.2017.106

Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs) has been considered as a strategy to improve the locomotor deficits caused by traumatic spinal cord injury (SCI). To date, enormous efforts have been made to derive OPCs from human pluripotent stem cells (hPSCs), and significant progress in the transplantation of such cells in SCI animal models has been reported. The current methods generally require a long period of time (>2 months) to obtain transplantable OPCs, which hampers their clinical utility for patients with SCI. Here we demonstrate a rapid and efficient method to differentiate hPSCs into neural progenitors that retain the features of OPCs (referred to as OPC-like cells). We used cell sorting to select A2B5-positive cells from hPSC-derived neural rosettes and cultured the selected cells in the presence of signaling cues, including sonic hedgehog, PDGF and insulin-like growth factor-1. This method robustly generated neural cells positive for platelet-derived growth factor receptor-α (PDGFRα) and NG2 (~90%) after 4 weeks of differentiation. Behavioral tests revealed that the transplantation of the OPC-like cells into the spinal cords of rats with contusive SCI at the thoracic level significantly improved hindlimb locomotor function. Electrophysiological assessment revealed enhanced neural conduction through the injury site. Histological examination showed increased numbers of axon with myelination at the injury site and graft-derived myelin formation with no evidence of tumor formation. Our method provides a cell source from hPSCs that has the potential to recover motor function following SCI.
Spinal injury: Stimulating stem cells for repair
A quick route to make cells that may repair spinal cord injuries moves researchers closer to the goal of treatments for paralysis in humans. Oligodendrocyte precursor cells (OPCs) generate the oligodendrocyte cells that build the insulating myelin sheaths around nerve fibers. They are believed to have potential for repairing damaged spinal cords, but difficulties producing them have hampered their application in clinical tests. Researchers in South Korea led by Joong Woo Leem and Dong-Wook Kim at Yonsei University have developed a rapid and efficient method to make OPC-like cells from human stem cells. The method selectively identifies and isolates suitable stem cells that can then be converted to OPC-like cells by treatment with signaling proteins and growth factors. Animal trials have shown the transplanted cells can partially repair spinal cord injuries without harmful side effects.