Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells

Abstract

The stromal vascular fraction (SVF) in adipose tissue contains a pool of various stem and progenitor cells, but the existence of hematopoietic stem and progenitor cells (HSPCs) in the SVF has not been seriously considered. We detected the presence of HSPCs in the SVF by phenotypically probing with Lin ؊ Sca-1 ؉ c-kit ؉ (LSK) and functionally confirming the presence using colony-forming cell assay and assessing the long-term multilineage reconstitution ability after SVF transplantation. The LSK population in the SVF was 0.004% plus or minus 0.001%, and 5 ؋ 10 5 freshly isolated SVF cells gave rise to 13 plus or minus 4 multilineage colonies. In addition, 0.15% plus or minus 0.03% of SVF cells was home to bone marrow (BM), especially near vascular and endosteal regions, 24 hours after blood transplantation. SVF transplantation was capable of generating a longterm (> 16 weeks), but variable extent (2.1%-32.1%) multilineage reconstitution in primary recipients, which was subsequently transferred to the secondary recipients by BM transplantation. All HSPCs within the SVF originated from the BM. Furthermore, the granulocyte-colonystimulating factor (G-CSF) mobilization of HSPCs from BM markedly elevated the number of phenotypic and functional HSPCs in the SVF, which induced a high efficiency long-term reconstitution in multilineage hematopoiesis in vivo. Our results provide compelling evidence that adipose tissue is a novel extramedullary tissue possessing phenotypic and functional HSPCs. (Blood. 2010;115:957-964) IntroductionHematopoietic stem and progenitor cells (HSPCs) in the complicated hierarchy of the hematopoietic system maintain themselves and generate many kinds of blood cells throughout life. To maintain their proper functioning, HSPCs reside in a special microenvironment called a niche. [1][2][3] Bone marrow (BM) is a dominant organ possessing a niche for HSPCs during adulthood. It is well known that a small fraction of HSPCs constantly circulate between the BM and peripheral blood without any stimulation. 4,5 The exiting and re-entering of HSPCs is mediated by interactions between several surface molecules, such as selectins and integrins. 1 In principle, on the way from peripheral blood back to the BM, HSPCs can settle down if the proper environment is provided. Supporting this concept, several extramedullary tissues were identified as HSPC-containing organs, including the liver, 6 spleen, 7 muscle, 8,9 and thoracic duct. 10 Among these organs, the liver and spleen are well-known locations for extramedullary hematopoiesis. 1 In both tissues, HSPCs reside close to sinusoidal endothelial cells, which may provide a preferential microenvironment. 6,11 The mechanism underlying HSPC maintenance in these extramedullary organs remains unclear, though the HSPCs still conserve their function properly. [6][7][8][9][10] Adipose tissues contain many different types of adult stem cells that can be used for therapeutic purposes, especially for tissue regeneration. 12 Adipose tissue is composed of lipid-filled mature ad...

Adipose Tissue as a Dedicated Reservoir of Functional Mast Cell Progenitors

“…The presence of immature hematopoietic cells in adipose tissue has been already demonstrated [2,3]. However, none of these studies demonstrated their multilineage hematopoietic differentiation.…”

“…HSPC described previously in WAT [3], were sorted based on the expression of cell surface markers (c-Kit þ /Thy-1 lo /Lin -/Sca þ ). Total BM cells and BM-derived HSPC were used as positive controls.…”

“…This cell population is known to consist of various cell types, including a large proportion of immune/hematopoietic cells. Indeed, it has been proposed that the adipose-derived hematopoietic compartment contains immature cells, able to rescue lethally irradiated mice [2], and to generate multilineage hematopoiesis in vitro [3]. In addition, the presence of numerous mature immune cells has been described including macrophages and lymphocytes that have been largely involved in the inflammatory process linked to the onset of obesity and type II diabetes [4][5][6][7].…”

Human peripheral blood-born hematosphere as a niche for hematopoietic stem cell expansion

“…However, we could not find dominance of a specific lineage, which would suggest graft-versus-host-disease or malignant transformation. Interestingly, when we isolated MNCs from other potential homing sites, including liver, spleen, kidney and adipose tissue [7], we found higher percentage of human hematopoietic cell chimerism than in bone marrow or peripheral blood (Supplementary information, Figure S5). The above results confirm the existence of long-term SCID repopulating cells (SRCs) derived from unmobilized adult peripheral blood through BBHS spheres.…”

Preliminary Clinical Results With Lipoaspirate Stromal Vascular Cell Fraction in Treatment of Patients With Knee Osteoarthritis

“…Одним из основ-ных преимуществ СВФ по сравнению с «чисты-ми» популяциями стволовых/стромальных кле-ток, полученных в результате культивирования in vitro, является гетерогенность этой фракции. Действительно, наряду с МСК, в образцах СВФ присутствуют различные типы клеток, оказы-вающих стимулирующий эффект на процессы регенерации и реваскуляризации и обладающих противовоспалительными и иммуномодулирую-щими свойствами (преадипоциты, предшествен-ники эндотелиальных клеток, макрофаги второго типа и Т-регуляторные клетки) [4,14,27]. Со-гласно критериям, разработанным International Federation for Adipose Therapeutics and Science (IFATS) и International Society for Cellular Therapy (ISCT), клетки СВФ должны иметь жизнеспо-собность не ниже 70% и экспрессировать следу-ющий иммунофенотип: CD13 + , CD29 + , CD44 + , CD73 + , CD90 + (> 40%), CD34 + (> 20%), CD31 + (< 20%) и CD45 + (< 50%) [4].…”