Physical impacts of PLGA scaffolding on hMSCs: Recovery neurobiology insight for implant design to treat spinal cord injury.

Autor: Han IB; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA; Division of SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA, USA., Thakor DK; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA; Division of SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA, USA., Ropper AE; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA; Division of SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA, USA., Yu D; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA; Division of SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA, USA., Wang L; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA; Division of SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA, USA., Kabatas S; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA; Division of SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA, USA., Zeng X; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA; Division of SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA, USA., Kim SW; Division of Periodontology, Harvard School of Dental Medicine, Boston, MA, USA., Zafonte RD; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA., Teng YD; Departments of Physical Medicine & Rehabilitation and Neurosurgery, Harvard Medical School/Spaulding Rehabilitation Hospital/Brigham and Women's Hospital, Boston, MA, USA; Division of SCI Research, Veterans Affairs Boston Healthcare System, Boston, MA, USA. Electronic address: yang_teng@hms.harvard.edu.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2019 Oct; Vol. 320, pp. 112980. Date of Electronic Publication: 2019 Jun 20.
DOI: 10.1016/j.expneurol.2019.112980
Abstrakt: Our earlier work generated a powerful platform technology of polymeric scaffolding of stem cells to investigate and treat the injured or diseased central nervous system. However, the reciprocal sequelae between biophysical properties of the polymer and responses of the stem cell have not been examined in situ in lesioned spinal cords. We postulated that implantable synthetic scaffolds, acting through physical features, might affect donor cell behavior and host tissue remodeling. To test this hypothesis, poly(d,l-lactic-co-glycolic acid) (PLGA) in either low/soft or high/hard rigidity was fabricated for carrying adult human bone marrow mesenchymal stromal stem cells (hMSCs). The construct was transplanted into the epicenter of a rat model of acute T9-10 segmental hemisection to evaluate the effect of PLGA rigidity on the therapeutic potential and fate of hMSCs for neural repair. Compared to controls, only treatment with soft PLGA-scaffolded hMSCs significantly improved sensorimotor function via activation of recovery neurobiology mechanisms. The main benefits included inhibiting neuroinflammation and enhancing tissue protection. Also detected in the treated lesion region were expressions of neurotrophic and anti-inflammatory factors together with proliferation of endogenous neural stem cells, impacts likely derived from hMSCs' functional multipotency maintained by soft PLGA-scaffolding. Conversely, hard rigidity PLGA activated mechanotransduction and mesoderm lineage differentiation of hMSCs that ectopically produced bone, cartilage and muscle markers in neural parenchyma. The findings collectively suggested that the physical texture of polymeric scaffolds should be tailored for sustaining the stemness of hMSCs to constructively interact with the spinal cord for functional restoration.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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