## 1 Introduction  
The primary causes of disability worldwide are low back and neck pain [1]. Despite their prevalence and socioeconomic impact, long-term curative treatments for these disorders are lacking. Novel approaches are being explored to resolve this issue, mainly focusing on alleviation or reversal of intervertebral disc (IVD) degeneration [2, 3, 4]. IVD degeneration is a progressive pathology, involving a decrease in cell numbers and cell potency, primarily within the central nucleus pulposus (NP) of the IVD, resulting in a switch in extracellular matrix (ECM) production [5, 6]. Specifically, the initially proteoglycan-rich and type II collagen NP-ECM progressively turns into a type I collagen fibrotic tissue, undermining the IVD's biomechanical characteristics [7]. The responding loss in IVD integrity alters disc height, requiring compensation in other spinal components, thereby potentially leading to a variety of spinal disorders such as facet joint arthritis and spondylisthesis. Alternatively,the outer collagen layers, collectively termed the annulus fibrosus (AF), can similarly lose their integrity, thereby enabling disc bulging or complete AF rupture. Finally, in reaction to these degenerative changes, the native IVD cells secrete inflammatory factors, potentially stimulating nerve ingrowth, vascularization, and immunogenic cell influx in the normally avascular and un-inervated discs or sensitizing nearby nerve structures [8; 9; 10]. Collectively, these changes can trigger nociception and in severe cases, might result in debilitating pain and disability in patients [11; 12]. This vicious cycle of disc degeneration [6] has proven difficult to combat in a clinical setting. Conservative treatment generally involves pain medication or muscle relaxants, while surgical intervention at later stages of degeneration, involves removal of disc tissue (e.g., microdiscectomy) or replacement of the complete disc (e.g., arthrodesis or arthroplasty). These final stage interventions are costly, invasive, and come with a range of complications such as adjacent disc disease, surgical infections, etc. [13; 14]. Moreover, their effectiveness in alleviating pain also remains to be confirmed [15]. Moreover, a large treatment gap exists for disc degeneration associated with LBP in the mild to moderate range, for patients for which analgesics proved ineffective but are not yet indicated for surgery. The field of regenerative medicine promises a wide range of therapeutics that have been theorized to be effective against disc degeneration. A variety of therapeutic strategies are being explored, each aimed to support cells to regenerate the IVD, e.g., gene therapy [16], growth factor injection [17], biomaterial injection [18; 19], or tissue engineering [20; 21]. Farthest in its clinical development is cell therapy, a regenerative strategy in which _de novo_ cells are introduced directly into the IVD [2; 3]. There, transplanted cells can either integrate within the IVD and contribute to appropriate ECM production, or otherwise modulate endemic cells to change the catabolic/inflammatory state to a more anabolic one. Multiple animal studies [22] have suggested the ability to modulate disc degeneration and induce regeneration of its matrix composition [23; 24] and inflammatory environment [25]. In the last decade, a multitude of clinical trials reported initial results, confirming the safety of cell therapy and have suggested their ability to reduce pain and disability [2]. However, large-scale placebo-controlled trials are still highly anticipated [2]. The primary cell source being investigated for IVD regeneration are MSC [26]. MSC are advantageous due to their accessibility, expandability, and suggested limited immunogenicity [27]. These, in contrast to NP cells or other chondrogenic cells, which lose their potency during culture [28] and have limited and compromised tissue sources that present low cell yields [29].