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Generation of induced pluripotent stem cell lines from two unrelated individual...

Ribeiro, Marta; Martins, Sandra; Carvalho, Teresa; Furtado, Marta; Cabral, Joaquim M.S.; Brito, Dulce; Carmo-Fonseca, Maria; da Rocha, Simão T.

Familial hypertrophic cardiomyopathy (HCM) is the most common inherited heart condition. HCM patients show left ventricle hypertrophy without any associated loading conditions, being at risk for heart failure and sudden cardiac death. Two induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells obtained from two unrelated individuals, a 54-year-old male (F81) and a 44-ye...


Transcriptome profiling of human pluripotent stem cell‐derived cerebellar organ...

Silva, Teresa P.; Sousa-Luis, Rui; Fernandes, Tiago G.; Bekman, Evguenia; Rodrigues, Carlos A.V.; Vaz, Sandra H.; Moreira, Leonilde M.; Hashimura, Yas

Human-induced pluripotent stem cells (iPSCs) have great potential for disease modeling. However, generating iPSC-derived models to study brain diseases remains a challenge. In particular, the ability to recapitulate cerebellar development in vitro is still limited. We presented a reproducible and scalable production of cerebellar organoids by using the novel single-use Vertical-Wheel bioreactors, in which funct...


Design and operation of a fully controlled platform for the production and puri...

Fernandes, Ana; Rosa, Sara; Silva, Ricardo; Cunha, Raquel; Fuzeta, Miguel Almeida; Calado, Cecília; Carvalho, Carla; Cabral, Joaquim M.S.; Azevedo, Ana

Currently, the production of extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSC) is performed in laborious and time-consuming static culture systems using serum-containing media, and their purification is through ultracentrifugation based methods. The whole process lacks on resolution, selectivity and capacity. Additionally, several differences were observed, in terms of the cargo of EVs, ...


Development of scalable processes to produce therapeutic mesenchymal stromal ce...

Cunha, Raquel M. S.; Vargas, Elga; Pires, Filipa; Calado, Cecília; Cabral, Joaquim M.S.; Silva, Cláudia; Fernandes, Ana

In summary, this study contributes to the establishment of a scalable process for MSC-EV production.


Evaluating the impact of culture conditions on human mesenchymal stromal cell-d...

Fernandes, Ana; Pereira, Maria; Ramalhete, Luís; Aleixo, Sandra; Silva, Cláudia; Cabral, Joaquim M.S.; Calado, Cecília

This work is a step forward into understanding how different culture conditions affect MSC-derived EVs characteristics.


Scaling-up the manufacturing of well-characterized mesenchymal stromal cell-der...

Fernandes, Ana; Rosa, Sara; Silva, Ricardo; Cunha, Raquel M. S.; Fuzeta, Miguel de Almeida; Calado, Cecília; Carvalho, Carla; Cabral, Joaquim M.S.

The platform established herein could be applied to the production of well-characterized SPC-EVs targeting their biomedical use in different settings (e.g. as drug delivery systems), as well as EVs from other parental cells lines (i.e. dendritic cells) in therapeutic settings as cancer.


Scalable production of human mesenchymal stromal cell-derived extracellular ves...

Fuzeta, Miguel de Almeida; Bernardes, Nuno; Oliveira, Filipa D.; Costa, Ana Catarina; Fernandes-Platzgummer, Ana; Farinha, José Paulo

Mesenchymal stromal cells (MSC) hold great promise for tissue engineering and cell-based therapies due to their multilineage differentiation potential and intrinsic immunomodulatory and trophic activities. Over the past years, increasing evidence has proposed extracellular vesicles (EVs) as mediators of many of the MSC-associated therapeutic features. EVs have emerged as mediators of intercellular communication...


Modeling Rett syndrome with human patient-specific forebrain organoids

Gomes, Ana Rita; Fernandes, Tiago G.; Vaz, Sandra H.; Silva, Teresa P.; Bekman, Evguenia; Xapelli, Sara; Duarte, Sofia; Ghazvini, Mehrnaz

Engineering brain organoids from human induced pluripotent stem cells (hiPSCs) is a powerful tool for modeling brain development and neurological disorders. Rett syndrome (RTT), a rare neurodevelopmental disorder, can greatly benefit from this technology, since it affects multiple neuronal subtypes in forebrain sub-regions. We have established dorsal and ventral forebrain organoids from control and RTT patient-...


Mesenchymal stromal cells induce regulatory T cells via epigenetic conversion o...

Azevedo, Rita I.; Minskaia, Ekaterina; Fernandes-Platzgummer, Ana; Vieira, Ana I. S.; da Silva, Cláudia Lobato; Cabral, Joaquim M.S.; Lacerda, João

Regulatory T cells (Treg) play a critical role in immune tolerance. The scarcity of Treg therapy clinical trials in humans has been largely due to the difficulty in obtaining sufficient Treg numbers. We performed a preclinical investigation on the potential of mesenchymal stromal cells (MSCs) to expand Treg in vitro to support future clinical trials. Human peripheral blood mononuclear cells from healthy donors ...


Impact of the human mesenchymal stem cells donor on conditional medium composition

Pereira, Maria João Canha; Ramalhete, Luís; Aleixo, Sandra; da Silva, Cláudia L.; Cabral, Joaquim M.S.; Calado, Cecília; Fernandes, Ana

Exosomes produced by Mesenchymal Stem Cells (MSCs) can represent a very appealing strategy for cell-free therapies. However, to achieve this reality it is necessary to further understand the process associated to the MSC culture when conditioned to produce exosomes. In the present work, it was evaluated how different MSC obtained from different donors may affect the conditioned media composition and how this ca...


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