Manufacturing of Placenta- and Umbilical Cord-Derived Mesenchymal Stromal Cells: A Systematic Scoping Review of Process Parameters, Quality Attributes, and Evidence-to-Control Relationships

Bolat Sadykov, Abay K. Baigenzhin, Anastasia Ganina, Madina Karimova, Aizhan Akhayeva, Anuar Zhunussov, Batyrbek Assembekov, Ildar Ravisovich Fakhradiyev

2026

Full text Open access: Gold Metadata (CSL-JSON)
DOI 10.3390/life16101740
Data confidence 70 medium
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Abstract

The manufacturing of placenta- and umbilical cord-derived mesenchymal stromal cells (MSCs) varies across anatomical starting material, isolation, culture supplementation, expansion, scale-up, cryopreservation, and release testing. This variability limits comparability between products and complicates process transfer. The study aimed to map full-text evidence on manufacturing variables, process outcomes, candidate critical material attributes (CMAs), candidate critical process parameters (CPPs), critical quality attributes (CQAs), potency assays, and release strategies for human placenta- and umbilical cord-derived MSCs. A systematic scoping review was conducted using a Population–Concept–Context framework and reported according to PRISMA-ScR, with search reporting guided by PRISMA-S. Searches without publication-date restrictions were completed on 15 August 2026. Two reviewers independently screened records and full texts, and charted data were independently verified. Findings were mapped by manufacturing contrast and outcome domain; quantitative pooling was considered only when biological, process, and methodological comparability supported an interpretable common effect estimate. The primary Scopus/Web of Science search identified 18,860 records; 13,122 unique records were screened and 439 full-text reports were assessed. After 208 exclusions, 231 manufacturing reports remained; the PubMed/MEDLINE search and backward/forward citation searching contributed two and five additional unique eligible reports, respectively, after cross-source deduplication, yielding 238 included reports. The study-family sensitivity set contained 236 distinct study families after linked-report assessment. Tissue-source coding identified 183 umbilical cord/Wharton’s jelly reports, 46 placental reports, and nine multi-source perinatal reports. The most frequent domains were expansion/passaging/senescence (94/238; 39.5%), media/supplements (69; 29.0%), isolation/tissue processing (67; 28.2%), and GMP/quality/release (48; 20.2%). Direct-comparison sets included 2D versus 3D/bioreactor expansion (23 reports), explant versus enzymatic isolation (22), fresh/native versus cryopreserved material (19), HPL versus FBS (12), and hypoxia versus normoxia (10). Differences in intervention definition, tissue compartment, passage/timepoint, endpoint, and unit did not support a coherent common pooled effect. The mapped evidence supports an end-to-end development model and does not identify a universal manufacturing recipe. Anatomical starting material, isolation, culture conditions, cumulative population doublings, scale-up, cryopreservation, and potency-linked release should be treated as interdependent elements of product comparability. Formal designation of CMAs and CPPs remains product- and platform-specific and requires evidence that links process variation to relevant CQAs.