Stromal Cell Subsets Directing Neonatal Spleen Regeneration

Tan, Jeff; Watanabe, Takeshi

doi:10.1038/srep40401

Cited by 19 publications

(27 citation statements)

References 35 publications

(52 reference statements)

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“…Engraftment of stromal fractions isolated by enrichment based on cell surface markers led to the identification of a spleen organizer cell as an endothelial‐like CD31 + MAdCAM‐1 + cell . However, formation of ectopic tissue was also found to be dependent on the presence of mesenchymal PDGFRb + cells . Stromal cell lines derived from long‐term cultures of the spleen, which support in vitro hematopoiesis, have also been grafted under the kidney capsule and shown to accumulate HSCs and myeloid cells from the host .…”

Section: Harnessing Emh In the Spleen To Improve Hsc Transplantation mentioning

confidence: 99%

Targeting the Spleen as an Alternative Site for Hematopoiesis

et al. 2019

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Bone marrow is the main site for hematopoiesis in adults. It acts as a niche for hematopoietic stem cells (HSCs) and contains non‐hematopoietic cells that contribute to stem cell dormancy, quiescence, self‐renewal, and differentiation. HSC also exist in resting spleen of several species, although their contribution to hematopoiesis under steady‐state conditions is unknown. The spleen can however undergo extramedullary hematopoiesis (EMH) triggered by physiological stress or disease. With the loss of bone marrow niches in aging and disease, the spleen as an alternative tissue site for hematopoiesis is an important consideration for future therapy, particularly during HSC transplantation. In terms of harnessing the spleen as a site for hematopoiesis, here the remarkable regenerative capacity of the spleen is considered with a view to forming additional or ectopic spleen tissue through cell engraftment. Studies in mice indicate the potential for such grafts to support the influx of hematopoietic cells leading to the development of normal spleen architecture. An important goal will be the formation of functional ectopic spleen tissue as an aid to hematopoietic recovery following clinical treatments that impact bone marrow. For example, expansion or replacement of niches could be considered where myeloablation ahead of HSC transplantation compromises treatment outcomes.

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Section: Harnessing Emh In the Spleen To Improve Hsc Transplantation mentioning

confidence: 99%

Targeting the Spleen as an Alternative Site for Hematopoiesis

et al. 2019

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“…For that, we used splenic stromal cells from neonatal rats, as these cells (and not lymphocytes) are fundamental for the regeneration of the spleen ( Tan and Watanabe, 2014 ). After, these authors ( Tan and Watanabe, 2017 ), identified that the stromal cell population MAdCAM-1 + CD31 + CD201 + is essential for the formation of new splenic tissues. Despite the complete regeneration of the splenic tissue, both studies used the renal capsule to transplant stromal cells individually, either due to the large local vascularization or due to the lack of ideal support for sowing the cells.…”

Section: Discussionmentioning

confidence: 99%

Decellularized Splenic Matrix as a Scaffold for Spleen Bioengineering

Zanardo

Amorim

Taufner

et al. 2020

Front. Bioeng. Biotechnol.

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The spleen is considered a non-essential organ. However, its importance is increasingly clear, given the serious disorders caused by its absence or dysfunction, e.g., greater susceptibility to infections, thromboembolism and cancer. Surgical techniques to preserve the spleen and maintain splenic function have become increasingly common. However, the morbidity and mortality associated with its absence and dysfunction are still high. We used the decellularization technique to obtain a viable splenic scaffold for recellularization in vitro and propose the idea of bioengineered spleen transplantation to the host. We observed the maintenance of important structural components such as white pulp, marginal zone and red pulp, in addition to the network of vascular ducts. The decellularized scaffold presents minimal residual DNA and SDS, which are essential to prevent immunogenic responses and transplantation failure. Also, the main components of the splenic matrix were preserved after decellularization, with retention of approximately 72% in the matrisomal protein content. The scaffold we developed was partially recellularized with stromal cells from the spleen of neonatal rats, demonstrating adhesion, proliferation and viability of cells. Therefore, the splenic scaffold is very promising for use in studies on spleen reconstruction and transplantation, with the aim of complete recovery of splenic function.

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“…MAdCAM-1-positive stromal cells were found to play an important role in spleen tissue organogenesis. 29 MZ B cells, which are the most frequent cell type contacting MAdCM-1+ stromal cells, recirculate between the spleen and gut-associated tissues, and may depend on MAdCAM-1+ stromal cells for their survival and activity regulation . 28 It was also suggested that the specialized stromal marginal reticular cells form a barrier inside the MZ, which guarantees the maintenance of gradients necessary for positioning of migratory B and T cells in the WP.…”

Section: Discussionmentioning

confidence: 99%