Evaluation of a cell-banking strategy for the production of clinical grade mesenchymal stromal cells from Wharton's jelly

Oliver-Vila, Irene; Coca, María Isabel; Grau-Vorster, Marta; Pujals-Fonts, Noèlia; Caminal, Marta; Casamayor-Genescà, A.; Ortega, Isabel; Reales, Laura; Pla, Arnau; Blanco, Miguel; Garcı́a, Joan; Vives, Joaquim

doi:10.1016/j.jcyt.2015.10.001

Cited by 47 publications

(45 citation statements)

References 34 publications

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“…Phycoerythrin (PE) (phycoerythrin) ‐conjugated immunoglobulin (Ig)G1 (X40; BD Biosciences) and fluorescein isothiocyanate (FITC)‐conjugated IgG2bk (27‐35; BD Biosciences) antibodies were used as isotype controls. Osteogenic potency of MSCs was tested in vitro using StemPro differentiation media (Gibco), and alkaline phosphatase (Takara Bio Inc., Toyobo, Japan) specific staining (Oliver‐Vila et al ., ).…”

Section: Methodsmentioning

confidence: 97%

“…Osteogenic potency of MSCs was tested in vitro using StemPro differentiation media (Gibco), and alkaline phosphatase (Takara Bio Inc., Toyobo, Japan) specific staining (Oliver-Vila et al, 2016).…”

Section: Isolation Of Cells Expansion Cultures and Cell Seeding Of Bmentioning

confidence: 99%

“…Both ovine and human tissues were harvested, fixed in 4% formalin at room temperature, decalcified in 5% formic acid (Decalcifier I; Surgipath Canada Inc., Winnipeg, Canada), and embedded in paraffin for subsequent histological and immunohistochemical procedures Oliver-Vila et al, 2016). Microtome sections 4 μm thick were either stained with H&E or immunostained for the detection of macrophages (CD68, KP-1; Dako, Glostrup, Denmark), and vessels (endothelial cells, CD31, JC70A, Dako), as reported elsewhere (Gomez-Puerta et al, 2013).…”

Section: Histological Processing and Immunostainingmentioning

confidence: 99%

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Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis

Prat

Gallardo-Villares

Vives

et al. 2017

J Tissue Eng Regen Med

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Pseudoarthrosis is a relatively frequent complication of fractures, in which the lack of mechanical stability and biological stimuli results in the failure of bone union, most frequently in humerus and tibia. Treatment of recalcitrant pseudoarthrosis relies on the achievement of satisfactory mechanical stability combined with adequate local biology. Herein we present two cases of atrophic pseudoarthrosis that received a tissue-engineering product (TEP) composed of autologous bone marrow-derived mesenchymal stromal cells (BM-MSC) combined with deantigenized trabecular bone particles from a tissue bank. The feasibility of the treatment and osteogenic potential of the cell-based medicine was first demonstrated in an ovine model of critical size segmental tibial defect. Clinical-grade autologous BM-MSC were produced following a good manufacturing practice-compliant bioprocess. Results were successful in one case, with pseudoarthrosis resolution, and inconclusive in the other one. The first patient presented atrophic pseudoarthrosis of the humeral diaphysis and was treated with osteosynthesis and TEP resulting in satisfactory consolidation at month 6. The second case presented a recalcitrant pseudoarthrosis of the proximal tibia and the Masquelet technique was followed before filling the defect with the TEP. This patient presented a neuropathic pain syndrome unrelated to the treatment that forced the amputation of the extremity 3 months later. In this case, the histological analysis of the tissue formed at the defect site provided evidence of neovascularization but no overt bone remodelling activity. It is concluded that the use of expanded autologous BM-MSC to treat pseudoarthrosis was demonstrated to be feasible and safe, provided that no clinical complications were reported, and early signs of effectiveness were observed.

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Section: Methodsmentioning

confidence: 97%

Section: Isolation Of Cells Expansion Cultures and Cell Seeding Of Bmentioning

confidence: 99%

Section: Histological Processing and Immunostainingmentioning

confidence: 99%

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Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis

Prat

Gallardo-Villares

Vives

et al. 2017

J Tissue Eng Regen Med

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“…Cell diameter, cell volume and total cell count was determined using the Scepter Handhelp Automated Cell Counter (Millipore, Darmstadt, Germany). Cumulative population doublings (CPD) were determined as CPD = [ln (initial cell density/final cell density)]/ln2 (Oliver‐Vila et al, ). For the manufacture of cell–scaffold composites, 6 × 10 6 MSCs were inoculated together with 1 cm 3 of trabecular bone particles (Osteoplant, Bioteck, Vicenza, Italy) in a single‐use vessel taken from the Hexascreen bioreactor system (Hexascreen Culture Technologies S.L.)…”

Section: Methodsmentioning

confidence: 99%

A reproducible method for the isolation and expansion of ovine mesenchymal stromal cells from bone marrow for use in regenerative medicine preclinical studies

Caminal

Vélez

Rabanal

et al. 2016

J Tissue Eng Regen Med

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The use of multipotent mesenchymal stromal cells (MSCs) as candidate medicines for treating a variety of pathologies is based on their qualities as either progenitors for the regeneration of damaged tissue or producers of a number of molecules with pharmacological properties. Preclinical product development programmes include the use of well characterized cell populations for proof of efficacy and safety studies before testing in humans. In the field of orthopaedics, an increasing number of translational studies use sheep as an in vivo test system because of the similarities with humans in size and musculoskeletal architecture. However, robust and reproducible methods for the isolation, expansion, manipulation and characterization of ovine MSCs have not yet been standardised. The present study describes a method for isolation and expansion of fibroblastic-like, adherent ovine MSCs that express CD44, CD90, CD140a, CD105 and CD166, and display trilineage differentiation potential. The 3-week bioprocess proposed here typically yielded cell densities of 1.4 × 10 MSCs/cm at passage 2, with an expansion factor of 37.8 and approximately eight cumulative population doublings. The osteogenic potential of MSCs derived following this methodology was further evaluated in vivo in a translational model of osteonecrosis of the femoral head, in which the persistence of grafted cells in the host tissue and their lineage commitment into osteoblasts and osteocytes was demonstrated by tracking enhanced green fluorescent protein-labelled cells. Copyright © 2016 John Wiley & Sons, Ltd.

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“…Availability of these clinical‐grade cell lines will allow researchers to differentiate tissue‐specific stem cell progenitors. A second interesting project is the mesenchymal stem cell bank . Wharton's Jelly‐derived mesenchymal stromal cells have the potential to be used in several different situations: GVHD treatment, heart regeneration with direct perfusion or through generation of tissue and cell composites, neural regeneration in spinal cord section, Crohn's fistula, and many others.…”

Section: Other Uses Of the Cord Blood Inventoriesmentioning

confidence: 99%

Rapid review: next generation of cord blood banks; transplantation and beyond

Querol

Samarkanova

2019

Transfusion

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Evaluation of a cell-banking strategy for the production of clinical grade mesenchymal stromal cells from Wharton's jelly

Cited by 47 publications

References 34 publications

Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis

Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis

A reproducible method for the isolation and expansion of ovine mesenchymal stromal cells from bone marrow for use in regenerative medicine preclinical studies

Rapid review: next generation of cord blood banks; transplantation and beyond

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