ISO/TS 22859:2022

Biotechnology — Biobanking — Requirements for human mesenchymal stromal cells derived from umbilical cord tissue

This document specifies requirements for the biobanking of human mesenchymal stromal cells derived from umbilical cord tissue (i.e. Wharton’s jelly), further referred to as hUC-MSCs, including the collection of umbilical cord tissue and associated data, isolation, culture characterization, quality control, cryopreservation, storage, thawing, disposal, distribution and transport. This document is applicable to all organizations performing biobanking of hUC-MSCs used for research and development. This document does not apply to hUC-MSCs for the purpose of in vivo application in humans, clinical applications or therapeutic use. NOTE International, national or regional regulations or requirements, or multiple of them, can also apply to specific topics covered in this document.

Biotechnologie — Banques biologiques — Exigences relatives aux cellules stromales mésenchymateuses humaines issues des tissus du cordon ombilical

General Information

• Status: Published
• Publication Date: 19-Jul-2022
• ICS: 07.080 - Biology. Botany. Zoology
• Technical Committee: ISO/TC 276 - Biotechnology
• Drafting Committee: ISO/TC 276/WG 2 - Biobanks and bioresources
• Current Stage: 6060 - International Standard published
• Start Date: 20-Jul-2022
• Due Date: 09-Jul-2022
• Completion Date: 20-Jul-2022

Standards Content (Sample)

TECHNICAL ISO/TS
SPECIFICATION 22859
First edition
2022-07
Biotechnology — Biobanking
— Requirements for human
mesenchymal stromal cells derived
from umbilical cord tissue
Biotechnologie — Banques biologiques — Exigences relatives aux
cellules stromales mésenchymateuses humaines issues des tissus du
cordon ombilical
Reference number
ISO/TS 22859:2022(E)
© ISO 2022

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ISO/TS 22859:2022(E)
COPYRIGHT PROTECTED DOCUMENT
© ISO 2022
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting on
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Published in Switzerland
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ISO/TS 22859:2022(E)
Contents Page
Foreword .v
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviated terms and symbols .5
5 General requirements .10
5.1 General . 10
5.2 Personnel, facilities and equipment . 10
5.3 Reagents, consumables and other supplies . 11
5.4 Management of information and data . 11
6 Collection of umbilical cord and associated data .11
6.1 Information about the umbilical cord donor . 11
6.2 Collection procedure .12
7 Transport of umbilical cord or hUC-MSCs and associated data to the biobank .13
8 Reception and traceability of umbilical cord tissue or hUC-MSCs and associated data .13
9 Isolation and expansion of hUC-MSCs .13
9.1 Processes .13
9.2 Unique identification . 13
9.3 Testing for infectious agents . 14
9.4 Isolation of hUC-MSCs and primary culture . 14
9.5 Subculture and limited expansion . 14
10 Characterization of hUC-MSCs .14
10.1 General . 14
10.2 Viability . 15
10.3 Morphology . 15
10.4 Population doubling time and subculture/passage. 16
10.4.1 PDT . 16
10.4.2 Subculture/passage . 16
10.5 Cell population purity . 16
10.6 In vitro self-renewal assessment . 17
10.7 Proliferation . 17
10.8 Differentiation capability — In vitro multilineage differentiation . 17
10.8.1 General . 17
10.8.2 In vitro adipogenic differentiation . 17
10.8.3 In vitro chondrogenic differentiation . 18
10.8.4 In vitro osteogenic differentiation . 18
10.9 Immunophenotyping by flow cytometry . 18
10.10 Paracrine secretion/expression (protein-based assay of secretome) .20
10.11 Immunoregulation (modulation of immune cells) . 20
10.12 Microbial contamination . 21
11 Quality control .21
12 Storage .22
13 Thawing .23
14 Disposal .24
15 Distribution of hUC-MSCs — Information for users .24
16 Transport of hUC-MSCs .24
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ISO/TS 22859:2022(E)
16.1 General . 24
16.2 hUC-MSCs frozen in ampoules or cryovials . 25
16.3 Living hUC-MSC cultures . 25
Annex A (informative) Exemplary quality control test procedure for biobanking of hUC-
MSCs .27
Annex B (informative) Examples for suitable methods for the isolation and primary culture
of hUC-MSCs .28
Annex C (informative) Exemplary methods for characterization of hUC-MSCs .30
Bibliography .32
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ISO/TS 22859:2022(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO’s adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see www.iso.org/
iso/foreword.html.
This document was prepared by Technical Committee ISO/TC 276, Biotechnology.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.
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ISO/TS 22859:2022(E)
Introduction
Mesenchymal stromal cells are a heterogeneous cell population that is characterized by multiple
[8]
functional properties including the ability to secrete paracrine factors, regulate immune effector
[9][10] [11][12]
cells, maintain primitive phenotypes of other cell populations and support tissue
[13][14]
regeneration. Mesenchymal stromal cells can contain a sub-population of stem or progenitor cells
that demonstrate in vitro self-renewal and differentiation, as has been rigorously demonstrated for
[15]
umbilical cord-derived progenitor cells.
[16]
Mesenchymal stromal cells and mesenchymal stem cells are both abbreviated as “MSCs”. For the
purpose of this document, the abbreviated term “MSCs” refers to mesenchymal stromal cells.
The functional definition of MSCs has evolved over time as the biology of these cells is better understood.
Despite these advances, substantial ambiguities persist regarding the nomenclature, nature, identity,
function, mode of isolation and experimental handling of these cells. MSCs are not fully defined by the
[17]
initial minimal criteria proposed by the International Society of Cell and Gene Therapy (ISCT), and
[16]
as such require careful characterization by a matrix of functional assays.
[15] [18][19]
MSCs have been isolated from umbilical cord , bone marrow and other tissue sources, and are
widely used for non-clinical research. MSCs from different tissue sources have different properties.
Different institutions use different practices for isolating, processing and biobanking these MSCs,
making it difficult to compare data and results across institutions. Thus, there is a need for standardized
approaches to isolate, process, expand and cryopreserve these MSCs from specific tissue sources.
This document provides requirements for biobanking of human mesenchymal stromal cells derived
from umbilical cord tissue (Wharton’s jelly) (hUC-MSCs) for research purposes. This document is
applicable for academic centres, public and private institutions performing a biobanking service of
hUC-MSCs for research and development (R&D) and preclinical studies, not for clinical use.
Importantly, this document is focused on MSCs that have been isolated, manipulated and/or propagated
from umbilical cord tissue (also called “Wharton’s jelly”) in culture for research purposes. These cells
are different from unmanipulated cells found in human umbilical cord tissue (Wharton’s jelly).
[20]
ISBT 128 provides terminology and abbreviations for all medicinal products including cell therapy,
and abbreviates these as “MSC(WJ)” to denote mesenchymal stromal cells from Wharton’s jelly. This
document recognizes this abbreviation, but uses the more commonly-used convention in research to
denote human mesenchymal stromal cells derived from umbilical cord tissue (Warton’s jelly) (hUC-
[21]
MSCs).
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TECHNICAL SPECIFICATION ISO/TS 22859:2022(E)
Biotechnology — Biobanking — Requirements for human
mesenchymal stromal cells derived from umbilical cord
tissue
1 Scope
This document specifies requirements for the biobanking of human mesenchymal stromal cells
derived from umbilical cord tissue (i.e. Wharton’s jelly), further referred to as hUC-MSCs, including
the collection of umbilical cord tissue and associated data, isolation, culture characterization, quality
control, cryopreservation, storage, thawing, disposal, distribution and transport.
This document is applicable to all organizations performing biobanking of hUC-MSCs used for research
and development.
This document does not apply to hUC-MSCs for the purpose of in vivo application in humans, clinical
applications or therapeutic use.
NOTE International, national or regional regulations or requirements, or multiple of them, can also apply to
specific topics covered in this document.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 8601-1, Date and time — Representations for information interchange — Part 1: Basic rules
ISO 20387:2018, Biotechnology — Biobanking — General requirements for biobanking
ISO 21709:2020, Biotechnology — Biobanking — Process and quality requirements for establishment,
maintenance and characterization of mammalian cell lines
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 20387:2018, ISO 21709:2020
and the following apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1
authenticity
quality of being genuine or true
3.2
biobank
legal entity or part of a legal entity that performs biobanking (3.3)
[SOURCE: ISO 20387:2018, 3.5]
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ISO/TS 22859:2022(E)
3.3
biobanking
process of acquisitioning and storing, together with some or all of the activities related to collection,
preparation, preservation, testing, analysing and distributing defined biological material as well as
related information and data
[SOURCE: ISO 20387:2018, 3.6]
3.4
biorisk
effect of uncertainty expressed by the combination of the consequences of an event (including changes
in circumstances) and the associated “likelihood” (as defined in ISO Guide 73) of occurrence, where
biological material is the source of harm
Note 1 to entry: The harm can be the consequence of an unintentional exposure, accidental release or loss, theft,
misuse, diversion, unauthorized access or intentional unauthorized release.
[SOURCE: ISO 35001:2019, 3.17]
3.5
cell culture
growth of cells dissociated from the parent tissue by spontaneous migration, mechanical or enzymatic
dispersal for propagation under in vitro conditions
3.6
cell master file
complete dossier of all procedures and records used to generate a cell
3.7
cell morphology
form and structure of the cell
Note 1 to entry: Morphology can be represented by a single parameter or a combination of two or more
parameters.
[SOURCE: ISO 21709:2020, 3.3]
3.8
cell population purity
percentage of a particular cell type in a population, of which has the same specific biological
characteristics, such as cell surface markers, genetic polymorphisms and biological activities
3.9
colony forming unit fibroblast
CFU-F
typical in vitro assay to demonstrate self-renewal (3.23) potential of progenitor cells plated at low
frequencies that results in a formation of a colony of fibroblast-looking cells
Note 1 to entry: A count of these colonies is instructive of the colony forming potential or in vitro self-renewal
capacity of these cells.
3.10
cryopreservation
process by which cells are maintained in an ultra-low temperature in an inactive state so that they can
be revived later
[SOURCE: ISO 21709:2020/Amd 1:2021, 3.6]
3.11
differentiation
process to bring the cells into a defined cell state or fate
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ISO/TS 22859:2022(E)
3.12
differentiation potential
ability that refers to the concept that stem and progenitor cells can produce daughter cells which are
able to further differentiate into other cell types
3.13
flow cytometry
methodologically oriented subdiscipline of analytical cytology that measures cells in suspension in a
liquid vehicle as they pass, typically one cell at a time, by a measurement station
Note 1 to entry: The measurement represents transformations of changes in the output of a detector (or
detectors) due to changes in scattered light, absorbed light, light emitted (fluorescence) by the cell, or changes in
electrical impedance, as the cell passes through the measuring station.
Note 2 to entry: Flow cytometry allows simultaneous evaluation of morphological characteristics of cells (size
and internal complexity) with membrane or intracellular antigens.
[SOURCE: CLSI H44 -A2: 2004, Clause 4, modified — Note 2 to entry has been added.]
3.14
heterogeneity
non-uniformity of composition, quality or structure of a population of cells
3.15
homogeneity
uniformity of composition, quality or structure of a population of cells
3.16
human mesenchymal stromal cell derived from umbilical cord tissue
hUC-MSC
heterogeneous cellular population isolated from umbilical cord (3.25), which has the ability to
modulate the immune response, secrete paracrine factors and undergo adipogenesis, osteogenesis and
chondrogenesis in vitro
Note 1 to entry: Without any manipulation, “culture-adapted MSCs” is an alternate term used to denote cells
that are different from cells that are found in vivo. It is increasingly clear that these cell types have different
properties in terms of gene expression, functionality and phenotype.
3.17
licensing
act of stimulating hUC-MSCs (3.16) using inflammatory cytokines to
become more immunosuppressive
Note 1 to entry: Licensing is a biological term and not a regulatory or legal term.
3.18
passage
subculture
process of further culturing of cells in a culture vessel to provide higher surface area/volume for the
cells to grow
Note 1 to entry: A passage can be performed by harvesting an aliquot from the parent vessel and reseeding it into
another vessel.
3.19
passage number
number of subculturing that occurred
Note 1 to entry: For this document, P is understood as the starting population of the cells.
0
[SOURCE: ISO 21709:2020, 3.13, modified — Note 1 to entry added.]
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ISO/TS 22859:2022(E)
3.20
population doubling time
PDT
doubling time
time taken for cultured cell count to double
Note 1 to entry: The time is measured in hours.
[SOURCE: ISO 21709:2020, 3.8, modified — “population doubling time” and “PDT” added as the preferred
term. Note 1 to entry added.]
3.21
primary culture
culture started from cells, tissues, or organs taken directly from an organism, and before the first
subculture, propagation and consecutive passages (3.18) in vitro
[SOURCE: ISO 21709:2020, 3.16, modified — Note 1 to entry deleted.]
3.22
proliferation
cell number expansion by cell division
3.23
self-renewal
ability of stem cells (3.24) to divide symmetrically, forming two identical daughter stem cells
Note 1 to entry: Adult stem cells can also divide asymmetrically to form one daughter cell, which can proceed
irreversibly to a differentiated cell lineage and ultimately lead to focused functional differentiated cells, while
the other daughter cell still retains the characteristics of the parental stem cell.
3.24
stem cell
non-specialized cells with the capacity for self-renewal (3.23) and differentiation potential (3.12), which
can differentiate into one or more different types of specialized cells
Note 1 to entry: Most adult stem cells are multipotent stem cells.
3.25
umbilical cord
umbilical cord tissue
UC
soft, gelatinous connective tissue (i.e. Wharton jelly), excluding umbilical arteries, umbilical vein and
placenta
3.26
viability
attribute of being alive (e.g. metabolically active, capable of reproducing, have intact cell membrane, or
have the capacity to resume these functions) as defined based on the intended use
[SOURCE: ISO 21709:2020, 3.17]
3.27
viable cells
cells within a sample that have an attribute of being alive (e.g. metabolically active, capable of
reproduction, possessed of intact cell membrane, or with the capacity to resume these functions)
defined based on the intended use
[SOURCE: ISO 20391-1:2018, 3.29]
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ISO/TS 22859:2022(E)
4 Abbreviated terms and symbols
2D1 clone of anti-human CD45 antibody
4F2 clone of anti-human CD98 antibody
561 clone of anti-human CD34 antibody
581 clone of anti-human CD34 antibody
58XB4 clone of anti-human CD104 antibody
63D3 clone of anti-human CD14 antibody
A20 tumour necrosis factor alpha-induced protein 3 (TNFAIP3)
ACAN aggrecan
AD2 anti-human CD-73 (Ecto-5’-nucleotidase) antibody
AHR aryl hrdrocarbon receptor
ALP alkaline phosphatase
ANGPT2 angiopoietin-2
AP2 adipocyte protein-2
α-SMA alpha-smooth muscle actin
B7RP2 B7-related protein 2
BCL-2 B-cell lymphoma 2
BJ18 clone of anti-human CD44 antibody
BM bone marrow
C44Mab-5 clone of anti-human CD44 antibody
CCL2 C-C Motif Chemokine ligand 2
CCL5 C-C Motif Chemokine ligand 5
CCL7 C-C Motif Chemokine ligand 7
CCR7 C-C Motif Chemokine receptor 7
CCR10 C-C Motif Chemokine receptor 10
CD clusters of differentiation
CD9 clusters of differentiation 9
CD13 clusters of differentiation 13
CD14 clusters of differentiation 14
CD29 clusters of differentiation 29
CD31 clusters of differentiation 31
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ISO/TS 22859:2022(E)
CD34 clusters of differentiation 34
CD44 clusters of differentiation 44
CD45 clusters of differentiation 45
CD46 clusters of differentiation 46
CD55 clusters of differentiation 55
CD73 clusters of differentiation73
CD90 clusters of differentiation 90
CD98 clusters of differentiation 98
CD104b clusters of differentiation 104b
CD105 clusters of differentiation 105
CD 146 clusters of differentiation146
CD276 clusters of differentiation 276
CEBPα enhancer-binding protein alpha
CFSE carboxyfluorescein succinimidyl ester
CFU colony forming units
human gene which encodes a protein called the class 2, major histocompatibility
CIITA
complex, transactivator
CO carbondioxide
2
COL2A1 collagen type 2 alpha 1
COX-2 prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2)
CX3CR1 C-3X-C Motif Chemokine receptor 1
CXCL9 C-X-C Motif Chemokine ligand 9
CXCL10 C-X-C Motif Chemokine ligand 10
CXCL11 C-X-C Motif Chemokine ligand 11
CXCL12 C-X-C Motif Chemokine ligand 12
CXCR1 C-X-C Motif Chemokine receptor type 1
CXCR4 C-X-C Motif Chemokine receptor type 4
CXCR6 C-X-C Motif Chemokine receptor type 6
DCN.70 anti-CD276 (B7-H3) antibody
DMEM Dulbecco’s modified eagle medium
DMEM-LG Dulbecco’s modified eagle medium low glucose
DMSO dimethyl sulfoxide
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ISO/TS 22859:2022(E)
DRAP-24 clone of anti-human CD9 antibody
EDTA ethylenediaminetetraacetic acid
ELISA enzyme-linked immunosorbent assay
FABP4 Fatty acid-binding protein 4
FACS fluorescence activating cell sorter
FBS fetal bovine serum
FRP-1 frizzled-related protein
GAL-1 galactose-1
HBsAg hepatitis B surface antigen
HBV hepatitis B virus
HCD14 clone of anti-human CD14 antibody
HCsAg hepatitis C surface antigen
HCV hepatitis C virus
HEL113 gene of vimentin
HGF hepatocyte growth factor
HI30 clone of anti-human CD45 antibody
HI9a clone of anti-human CD9 antibody
HIV human immunodeficiency virus
HLA human leukocyte antigen
HLA-Class I human leukocyte antigen – Class I
HLA-Class II human leukocyte antigen – Class II
HLA-DR human leukocyte antigen DR
HO-1 haem oxygenase-1
HSP70A heat shock protein 70A
HSP70B heat shock protein 70B
hUC-MSC human umbilical cord mesenchymal stromal cell
ICAM-1 intercellular adhesion molecule-1
IDO indoleamine 2,3-dioxygenase 1
IFN-γ interferon-gamma
IFU instructions for use
IL-1 interleukin-1
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ISO/TS 22859:2022(E)
IL-1RA interleukin-1 receptor antagonist
IL-6 interleukin-6
IL-8 interleukin-8
INCAM-110 inducible cell adhesion molecule 110
ITGB1 integrin 1 antibody
ITGB4 integrin 4 antibody
KGF keratinocyte growth factor
L243 clone of anti-human HLA-DR antibody
...